Treatment of malignant obstruction of the superior vena cava with the self-expanding Wallstent. Clinical outcome of stenting in superior vena cava syndrome associated with malignant tumors. Comparison with conventional treatment. Case report: superior vena cava obstruction complicated by central venous thrombosis--treatment with thrombolysis and Gianturco-Z stents. Superior vena cava obstruction in small-cell lung cancer. Gianturco-Rösch expandable Z-stents in the treatment of superior vena cava syndrome. [Endoprosthetic dilatation of the vena cava eliminates obstruction in superior vena cava syndrome]. [Stent implantation for the palliative therapy of upper inflow obstruction in bronchial carcinoma]. Superior vena caval obstruction due to small-cell anaplastic lung carcinoma. Response to chemotherapy. Resolution of superior vena cava obstruction in small cell lung cancer patients treated with chemotherapy. Superior vena caval obstruction syndrome in small cell lung cancer. Palliative effectiveness of radiation therapy in the treatment of superior vena cava syndrome. Case report: superior vena caval obstruction treated by thrombolysis, mechanical thrombectomy and metallic stents. [Venous angioplasty and Wallstent implantation in emergency treatment of superior vena cava syndrome caused by tumor]. Alternating versus sequential chemotherapy in small cell lung cancer. A randomized German multicenter trial. Superior vena cava stent placement: results with the Wallstent endoprosthesis. Percutaneous management of superior vena cava occlusions. Early closure of a multicenter randomized clinical trial of endoscopic stenting versus surgery for stage IV left-sided colorectal cancer. Stenting and superior vena caval syndrome. Intravascular stents in the management of superior vena cava syndrome. Alternating non-cross resistant chemotherapy for small cell lung cancer. Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: a randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG). Treatment of limited small-cell lung cancer with etoposide and cisplatin alternating with vincristine, doxorubicin, and cyclophosphamide versus concurrent etoposide, vincristine, doxorubicin, and cyclophosphamide and chest radiotherapy: a Southwest Oncology Group Study. [Cardioprotection in chemo- and radiotherapy for malignant diseases--an echocardiographic pilot study]. Phase III study comparing chemotherapy and radiotherapy with preoperative chemotherapy and surgical resection in patients with non-small-cell lung cancer with spread to mediastinal lymph nodes (N2); final report of RTOG 89-01. Radiation Therapy Oncology Group. Superior vena cava syndrome revisited. Small cell lung cancer with and without superior vena cava syndrome: a multivariate analysis of prognostic factors in 408 cases. Combined-modality treatment for resectable metastatic colorectal carcinoma to the liver: surgical resection of hepatic metastases in combination with continuous infusion of chemotherapy--an intergroup study. A randomized trial between two neoadjuvant chemotherapy protocols: CDDP + 5-FU versus CDDP + VP16 in advanced cancer of the head and neck. Induction chemotherapy in the treatment of patients with carcinoma of the esophagus. Treatment of obstruction of the superior vena cava by combination chemotherapy with and without irradiation in small-cell carcinoma of the bronchus. Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy--results of a multicentric randomized German trial in advanced head-and-neck cancer. Application of expandable metallic stents to the venous system. Randomized study comparing chemotherapy plus radiotherapy versus radiotherapy alone in FIGO stage IIB-III cervical carcinoma. GONO (North-West Oncologic Cooperative Group). Stent implantation in patients with superior vena cava syndrome. Pre-operative radiotherapy prolongs survival in operable esophageal carcinoma: a randomized, multicenter study of pre-operative radiotherapy and chemotherapy. The second Scandinavian trial in esophageal cancer. Combined chemotherapy and radiation therapy in advanced inoperable squamous cell carcinoma of the head and neck. The final report of a randomized trial. [Superior vena cava syndrome in microcytic carcinoma of the lung: incidence, treatment response and prognostic importance]. Thoracic radiation therapy alone compared with combined chemoradiotherapy for locally unresectable non-small cell lung cancer. A randomized, phase III trial. A randomized comparison of radiotherapy with a radiotherapy--chemotherapy combination in stage IV carcinoma of the head and neck.
Obstruction of the superior vena cava (SVC) in malignant disease can cause considerable distress to patients. Symptomatic relief can be achieved by the percutaneous implantation of a self-expanding stent (Wallstent) into the stenosis.
                Fourteen patients with obstruction of the SVC were treated with one to three Wallstent endoprostheses. They suffered from advanced bronchogenic carcinoma (n = 12), thyroid carcinoma (n = 1), and breast carcinoma (n = 1). The indication for stent placement was symptomatic obstruction of the SVC and incurable disease. Stenting was performed for symptom relief, and before, during, and after courses of radiotherapy or chemotherapy as needed.
                Twelve patients experienced complete symptomatic relief within two days of stent placement. Two patients did not benefit. Three patients not given anticoagulation developed stent thrombosis between one week and eight months after initial placement, and within one day of endobronchial stent implantation with bronchial laser therapy or balloon dilatation in all three. Patency of the SVC was achieved again by a repeat procedure.
                Stent placement for obstruction of the SVC gives rapid symptomatic relief. Subsequent endobronchial stent implantation with bronchial laser therapy or balloon dilatation could be a risk for caval stent occlusion. Stent thrombosis remains a problem in patients who are not anticoagulated. We analyzed the clinical outcome of treatment with the expandable metallic stent (EMS) for the superior vena cava (SVC) syndrome associated with malignant tumors, and the results were compared with those of radiotherapy.
                Of 33 patients with the SVC syndrome, 23 were treated by Gianturco EMS placement and 10 were treated by radiotherapy and/or chemotherapy alone. Of the 23 EMS patients, 11 had treatment before EMS placement and 12 had no treatment before EMS placement.
                After stenting, the clinical symptoms disappeared in 78% (18/23) of the patients, i.e. in 50% of the patients with intraluminal tumors, and in 93% of those with extrinsic compression. The clinical symptoms improved in 80% of patients who received radiotherapy. The mean duration of survival was 145 days in patients who underwent stenting, and 146 days in those receiving radiotherapy. However, the survival period differed significantly between patients with intraluminal tumors (44.9 days) and those with extrinsic compression (198.6 days). Between patients with previous treatment and those with no previous treatment, there was no significant difference in response rate or in survival period which were 82% versus 75%, and 127 days versus 162 days, respectively.
                The clinical symptoms showed similar improvement in patients receiving EMS placement or radiotherapy. EMS placement was effective in relieving clinical symptoms in patients who had failed to respond to radiotherapy. Expandable wire stents can provide effective palliation of superior vena cava obstruction (SVCO). We describe a case of SVCO unresponsive to radiotherapy and chemotherapy, which was complicated by extensive central venous thrombosis. Successful thrombolysis occurred with low-dose streptokinase allowing subsequent stent placement. To identify prognostic or treatment factors influencing the response of superior vena cava obstruction (SVCO), time to SVCO recurrence, and overall survival of SCLC patients with SVCO at presentation; and to assess the role of retreatment in patients with SVCO at recurrent or persistent disease.
                Between January 1983 and November 1993, 76 consecutive patients who had small-cell lung cancer (SCLC) with SVCO were treated in our institution. Analysis was done according to the disease status at diagnosis of SVCO. The first analysis concerned a group of 50 patients who had SVCO at initial presentation. The second analysis concerned a group who had SVCO as a manifestation of persistent or recurrent disease.
                In the first analysis, 93% had significant improvement in symptoms of SVCO after chemotherapy and 94% after mediastinal radiation. Response is almost universal despite a wide range of radiation fractionation and total dose used. Seventy percent remained SVCO-free before death. Thirty percent developed recurrence of SVCO symptoms 1-16 months (median 8) after the start of initial treatment. Those who received combined chemotherapy and radiation had a longer time to SVCO recurrence (p = 0.018) compared to those who received chemotherapy alone. This effect is mainly seen in limited-stage patients. The presence of SVCO recurrence tends to have an adverse effect on the overall survival (p = 0.077) irrespective of the time when the recurrences occurred (p = 0.296). The median survival of this whole group of 50 patients in the first analysis was 9.5 months, and the 2-year survival was 10%. Stage was strongly predictive of survival (p < 0.001). Sixteen percent (3 of 19) of the patients with limited-stage diseases were long-term survivors (two patients survived 35 months and one survived 70 months). The early mortality from SVCO was 2%. In the second analysis, 85% had previously been treated with chemotherapy alone. The response rate of SVCO in the analysable patients (n = 39) was 77%. There was no significant difference in the response rate of SVCO to treatment comparing patients treated by chemotherapy first or mediastinal radiation first (p = 0.653), but most patients [82% (32 of 39)] received radiation as the initially treatment of SVCO. Ninety-three percent (38 of 41) received mediastinal radiation as a part of their ultimate retreatment regimen, and 68% (28 of 41) received mediastinal radiation as their sole retreatment regimen. Thirty-two percent (13 of 41) received chemotherapy as a part of their ultimate retreatment regimen, and only 7% received chemotherapy alone as their sole retreatment regimen. Eighty-three percent (25 of 30) of those whose SVCO responded remained free of SVCO before death, with a median survival of 3 months after recurrent or persistent disease documented.
                Chemotherapy or mediastinal radiation is very effective as an initial treatment in SCLC patients with SVCO at presentation and at recurrent or persistent disease. There is no obvious need to use big radiation fraction sizes for the first few radiation treatment as was previously believed. In patients with recurrent or persistent SCLC with SVCO, especially in those who previously received chemotherapy only, we have more experience in incorporating mediastinal radiation as a major component of the palliative regimen with highly effective and durable palliation achieved. Gianturco-Rösch expandable Z-stents were used in 22 patients with superior vena cava syndrome (SVCS). Stents were placed in all patients in the SVC and in 17 patients, also into the innominate veins. Stent placement resulted in complete relief of symptoms in all patients. Twenty-one patients had no SVCS recurrence from 1 to 16 months, to their death, or to the present time. SVCS recurred only in 1 patient 9 months after stent placement due to tumor ingrowth and secondary thrombosis. Based on ours and on other reported experiences, expandable metallic stents are effective devices for treatment of the SVCS which is difficult to manage by other means. A 62-year-old woman with superior vena cava obstruction (SVCO) secondary to small cell lung cancer was treated with expandable wire stents prior to chemotherapy and irradiation. The treatment resulted in immediate and complete remission of the SVCO symptoms. To analyse results obtained in the palliative treatment of obstruction of the upper inflow veins by stent implantation in patients with bronchial carcinoma.
                Stents were implanted in 14 patients with upper venous obstruction due to bronchial carcinoma (three women, eleven men: mean age 64 [48-74] years), 4 of the superior vena cava (SVC), 6 of the SVC and brachiocephalic vein, 4 of the SVC and subclavian vein. To prevent thromboembolic phenomena all patients received heparin in therapeutic doses for 1-3 days from the time of stents implantation.
                Treatment was successful (regression of the clinical signs) in 12 of the 14 patients. Six patients died, without recurrence of the clinical signs, an average of 141 (10-420) days after the procedure. Mean survival time of the six patients who remained without symptoms was 3 months (longest interval 9 months). In one patient thrombotic occlusion of the SVC occurred 6 days after stent implantation. However, local thrombolysis successfully re-opened the vessel. Renewed upper vein obstruction occurred in two patients during follow-up. None of the stent filaments fractured and there was no stent dislocation.
                With a success rate of 86% stent implantation proved to be a sparing procedure in the palliative treatment of upper inflow vein obstruction, especially in patients with extensive malignant disease. Among 38 patients with bronchogenic carcinoma, small-cell type, eight patients had superior vena caval obstruction (SVCO) of recent onset. Seven of these patients were initially treated with combination chemotherapy (lomustine, cyclophosphamide, and methotrexate). One patient who had SVCO was treated initially by radiotherapy, with subsequent chemotherapy. In each patient, resolution of the syndrome was prompt, usually was complete by seven days, and was accompanied by objective tumor shrinkage. Symptoms of SVCO were transiently aggravated by the initiation of treatment in only one patient. In one individual treated by chemotherapy alone and in one treated by chemotherapy plus radiotherapy, SVCO recurred after initial control. Chemotherapy is an effective form of management of SVCO caused by small-cell carcinoma of the lung. Small cell lung cancer is a highly chemo-sensitive malignancy. As it often presents with a central lesion, superior vena cava obstruction (SVCO) is not an uncommon manifestation. From January 1990 to December 1993, 161 patients with small cell lung carcinoma were seen at our institution. Twenty (12.4%) of these patients presented with symptoms and signs of SVCO. Initial therapy consisted of radiotherapy in 4 patients and chemotherapy in 16 patients. Of those treated with chemotherapy, patient characteristics included 13 males, median age of 62.5 years (range 51 to 78 years), Eastern Co-operative Oncology Group (ECOG) performance status of 3 to 4 in 7 patients; 1 to 2 in 9 patients, and limited stage disease in 8 patients. The median period of follow-up was 5 months. Nine patients received a combination of cisplatin and etoposide (EP), 5 had cyclophosphamide, doxorubicin and vincristine, 1 had cyclophosphamide, etoposide and vincristine and 1 had monotherapy with oral etoposide. Overall response to chemotherapy was 81% (with 31% complete responses). All responders had resolution of SVCO. Only 3 patients did not respond (1 patient defaulted, 1 patient died of neutropenic sepsis at week one and 1 patient had stable disease). Resolution of SVCO was noted within the first 2 weeks after the first cycle; the earliest being 3 days. The only patient given single-agent oral etoposide responded within 10 days after initiation of treatment. Of the 7 patients with poor performance status (ECOG 3 to 4), 3 died from treatment-related complications. Chemotherapy is highly effective as a primary treatment of small cell lung carcinoma despite presentation with SVCO. However, caution is advised in the use of combination chemotherapy for those presenting with poor performance status. Initial therapy with oral etoposide or radiotherapy should be considered as possible alternatives for these patients. In a series of 643 patients with small cell lung cancer (SCLC), 55 patients (8.6%) had signs or symptoms of superior vena caval obstruction syndrome (SVCO). Relatively long intervals from the onset of the first symptoms of SVCO to the start of therapy were observed, and invasive diagnostic procedures were safely performed in most patients. The pretreatment characteristics of patients with SVCO were not significantly different from those of patients without signs of the syndrome, and survival was similar in both groups. Patients with SVCO were usually treated first with induction chemotherapy, and prompt resolution of signs and symptoms occurred in the majority. Radiation was effective in controlling SVCO at relapse or after failure of initial chemotherapy. It was concluded that SVCO in patients with SCLC should be treated initially with systemic chemotherapy, as for other presentations of this disease. The current data do not support the commonly held view that SVCO in SCLC should be approached as an oncologic emergency. A study was made of 34 patients concerning the palliation effect of radiation therapy in the treatment of superior vena cava syndrome (SVCS). They were seen between 1986-1993, at the Department of Radiotherapy in Middelheim General Hospital, Belgium, Antwerp. All patients had a syndrome of superior vena cava obstruction secondary to malignancy. The histologic diagnosis delivered an equal distribution of small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC). All patients with a SCLC received chemotherapy as initial treatment, but showed no response, relapse or evolution during treatment. Each treatment began with rapid-high dose irradiation, to continue after re-evaluation with rapid high-dose in cases of poor response or with the conventional fractionation of 2 Gy daily in patients showing good relief of symptoms. The initial rapid-high dose schedules depended on the performance status of the patients. Seventy-six percent of the patients with NSCLC showed good relief of their symptoms. It was very unexpected but the majority of NSCLC patients responded more quickly than SCLC patients, within three days after initiating treatment. In SCLC, 94% of the patients responded up until death. The palliation index defined as the ratio of the symptom-free period on the total survival which is 1 in ideal circumstances, was 0.55 in NSCLC and 0.90 in SCLC. In this last group, death was mainly due to disease progression in distant sites. We describe a case of superior vena caval obstruction (SVCO) due to bronchial carcinoma which was complicated by extensive central venous thrombosis. Partial clot lysis was achieved with thrombolytic agents, but therapy had to be discontinued due to bleeding from the gastrointestinal tract and puncture sites. Clot dissolution was completed using the Amplatz Thrombectomy Device, and the subsequent placement of a Gianturco Z-stent resulted in prolonged symptomatic relief. A 58-year-old man was hospitalized because of threatened asphyxia resulting from massive obstruction to neck vein flow and increased venous markings over the ventral and dorsal thorax. The previous year he had received radiotherapy (total of 55.8 Gy) for squamous cell carcinoma in the right upper lobe of the lung (primary stage T2 N2 M0). The signs of venous congestion had developed over several months.
                Emergency phlebography demonstrated obstruction to superior vena cava (SVC) flow by tumour compression.
                It was possible to pass the SVC obstruction with a hydrophilic guide-wire and then perform a balloon angioplasty, followed later by implantation of two intraluminal expandable stents ("Wallstent"). The dyspnoea quickly improved after the successful recanalization. The day after the intervention palliative radiotherapy of the SVC obstruction was begun. But increased venous markings over the thorax recurred, but without dyspnoea, after 4 1/2 months free of signs of venous congestion. Repeat phlebography again demonstrated complete obstruction of the SVC by the tumour. Recanalization by balloon angioplasty was again achieved.
                This case underlines the value of percutaneous balloon angioplasty with stent implantation as supplementary treatment in the late stages of SVC obstruction by tumour. A total of 306 patients with small cell lung cancer (SCLC) were randomized to receive chemotherapy in a sequential or alternating mode. Sequential chemotherapy consisted of eight cycles of cyclophosphamide, Adriamycin (doxorubicin), and vincristine (CAV) and alternating chemotherapy consisted of three cycles (1, 3, 5) of etoposide, vindesine, and ifosfamide (EVI); three cycles (2, 4, 6) of cisplatin, Adriamycin, and vincristine (PAV); and two cycles (7, 8) of cyclophosphamide, methotrexate, and CCNU (CMC). Responsive patients received prophylactic cranial irradiation after three cycles and chest irradiation after eight cycles of chemotherapy. No maintenance therapy was applied to patients achieving complete remission. Minimum follow-up was 2 years. Of the 302 patients evaluable, overall response rate was 59% in the sequential arm and 70% in the alternating arm. Patients treated with CAV had a complete response rate of 21% in contrast to 36% for those receiving alternating therapy. The median survival for all patients was 9.8 versus 11.3 months, for limited disease 11.1 versus 13.4 months, and for extensive disease 8.9 versus 9.9 months, all in favor of the alternating treatment. Two-year survival rate for all patients was 6% versus 9%, for limited disease 11% versus 14%, and for extensive disease 3% versus 6%, all preferring the alternating treatment mode. Progression-free survival demonstrated a strong correlation to the extent of response irrespective of the treatment regimen applied. Toxicity included 11 lethal and 8 life-threatening complications with a higher frequency in the alternating treatment arm. These results suggest that alternating treatment of SCLC with different drug combinations is more effective than sequential application of CAV. To assess the clinical success and short-term patency of the Wallstent endoprosthesis in the treatment of superior vena cava (SVC) syndrome.
                Twenty-one 14-mm-diameter endoprostheses were implanted in 15 patients (mean age, 60 years) treated for SVC syndrome due to malignant compression (n = 14) or postirradiation fibrotic stenosis (n = 1) of the SVC.
                Immediate technical success was achieved in all patients. Two early complications occurred: retroperitoneal hemorrhage due to venous iliac tear and early stent thrombosis. In the 14 patients without early stent occlusion, stent placement resulted in complete relief of SVC syndrome; clinical success was 93%. SVC syndrome did not recur from 1 to 14 months, until the patient died (n = 11) or until the end of the study (n = 3). Helical CT showed a patent stent in five patients, respectively, at 3, 6, 8, 10, and 11 months.
                SVC stent placement has good clinical results and a high patency rate at short-term follow-up in patients with SVC syndrome. To assess the use of percutaneous endovascular stent insertion in the management of superior vena cava (SVC) occlusion.
                Percutaneous endovascular stent insertion was attempted in 13 patients, age range 20-72 (mean 55.5) years, with symptomatic total occlusion of the SVC. Twelve patients had known malignant disease of the thorax. The other patient (age 20) had chronic SVC obstruction, the cause of which was unknown at the time of the procedure. There was initial angiographic assessment and removal of thrombus by thrombolysis (10 patients) and/or clot aspiration (3 patients). Following successful lysis or aspiration, single or multiple endovascular stents were inserted.
                The inability to cross the lesion with a guidewire prevented stent insertion in 2 patients (15.4%). There was primary success in the remaining 11 patients (84.6%), with associated symptomatic relief. Some recurrence of symptoms occurred in 5 of the 11 patients (45.5%) after a time interval ranging from 14 to 183 days. In all cases of symptomatic recurrence, patency was reestablished with further thrombolysis and/or further stent insertion. All successfully treated patients have since died. All 11 patients remained symptomatically free of SVC occlusion until death, with postprocedure survival ranging from 5 to 243 days.
                The percutaneous management of complete SVC occlusion with thrombolysis and/or clot aspiration followed by stent insertion is safe and effective, giving sustained symptomatic relief. The introduction of self-expandable metal stents has offered a promising alternative for palliation of malignant left-sided colonic obstruction. This randomized clinical trial aimed to assess whether a nonsurgical policy, with endoluminal stenting, is superior to surgical treatment in patients with stage IV left-sided colorectal cancer and imminent obstruction.
                Patients with incurable left-sided colorectal cancer who fulfilled the study criteria were randomly assigned to nonsurgical or surgical treatment. The primary outcome measure was survival in good health out of hospital (World Health Organization performance scores 0 or 1).
                A high number of serious adverse events in the nonsurgical arm led to premature closure of the trial. Ten patients were allocated to surgical treatment and 11 patients to nonsurgical palliation. The median survival in good health out of hospital during the first year was 56 days (interquartile range 7.5 - 338.5 days) in the surgical arm vs. 38 days (interquartile range 5.25 - 288.75 days) in the nonsurgical arm (P = 0.68). Eleven adverse events (six perforations) occurred in the nonsurgical arm vs. one adverse event in the surgical arm (P < 0.001). Of the six perforations, two were stent-related because they occurred at the proximal edge of the stent by erosion through a normal colon wall; one was probably stent-related (it was located in the region of the proximal half of the stent); one was a colon blowout; and two were late tumor perforations in patients on chemotherapy.
                The unexpected high rate of perforation in the nonsurgical arm might be specifically WallFlex-related or enteral stent-related in patients on chemotherapy and warrants attention. The use of intravascular stents in the management of Superior Vena Caval Obstruction is a relatively recent development. We describe our experience with six patients, aged between 64 and 85 years who developed SVC obstruction secondary to malignant disease and who had one or more intravascular stents inserted. Five of the patients had lung cancer and one metastatic breast carcinoma. Positive histology was available in three cases. A partial or complete clinical response was seen in all patients and two patients developed recurrent symptoms. Stenting appears to provide effective palliation of SVC obstruction symptoms. Superior vena cava syndrome can be effectively palliated with the use of intravascular stents. Adjunctive modalities which may be utilized prior to stent placement are thrombolytic therapy and balloon angioplasty. Six patients with an underlying malignancy were treated with these modalities. Complete resolution of symptoms occurred in five patients, and partial resolution occurred in the sixth. Two of the patients who had initial, complete resolution of symptoms had recurrences. One involved rethrombosis of the superior vena cava which occurred twice and required percutaneous thrombectomy, and the second involved restenosis requiring a percutaneous transluminal angioplasty of the SVC just distal to the stent. Both of these patients with second procedures, again, had complete resolution of symptoms. Intravascular stents are a valuable additional treatment of superior vena cava syndrome. After stratification for the extent of disease, previously untreated patients with small cell lung cancer randomized to receive therapy with the four-drug combination of cyclophosphamide, oncovin, nimustine hydrochloride (ACNU), and procarbazine (CONP) every four weeks (continuous regimen) or to receive CONP alternating with the three-drug combination of etoposide (VP-16), adriamycin and cisplatin (VAD) at four-week intervals (alternating regimen). Sixty-nine patients were entered in the study. Of 34 evaluable patients receiving the continuous regimen, six (17.6%) achieved complete response (CR) and 16 (47.1%) achieved partial response (PR). Of 31 evaluable patients receiving the alternating regimen, 10 (32.3%) achieved CR, and 16 (51.6%) achieved PR. There was a tendency in favor of the alternating regimen in CR and over-all response rates (0.05 less than p less than 0.1). There were no significant differences between the regimens in response duration or survival. The projected median survival times were 9.2 months and 9.4 months for the continuous and alternating regimens, respectively. One patient receiving the continuous regimen and three receiving the alternating regimen have been living for more than two years. The major toxicity was myelosuppression in both regimens. One patient died of hemorrhage due to thrombocytopenia during induction with CONP, and one patient died of cisplatin-induced renal failure. We conclude that alternating non-cross resistant chemotherapy leads to improved CR and response rates, but does not improve survival. Concurrent platinum etoposide chemotherapy given in combination with hyperfractionated thoracic radiation therapy (HTRT) in limited disease (LD) small cell lung cancer (SCLC) is associated with a high response rate and significant prolongation of survival. Given these results, the Hellenic Cooperative Oncology Group (HeCOG) performed a multicenter randomized phase II study in patients with LD SCLC to evaluate the timing of HTRT (early vs. late) when given concurrently with chemotherapy.
                To be eligible for the study, patients were required to have histologically or cytologically proven LD SCLC, confined to one hemithorax and/or ipsilateral mediastinal or supraclavicular lymphnodes and absence of pleural effusion or controlateral supraclavicular lymphnode involvement. Moreover, patients had to have a good performance status and adequate haematological, liver and renal function. Patients with LD SCLC were randomized to receive HTRT either concurrently with the first (Group A) or with the fourth (Group B) cycle of chemotherapy. Chemotherapy consisted of carboplatin administered at an AUC of six given as an i.v. 1-hour-infusion immediately followed by etoposide at a dose of 100 mg/m2 i.v. as a two-hour infusion for three consecutive days every three weeks up to a total of six cycles. Prophylactic cranial irradiation was also given to patients achieving a complete response.
                42 and 39 patients, were eligible for efficacy evaluation in group A and B respectively. The overall response rate was 76% in group A and 92.5% in group B (P = 0.07) with a complete response rate of 40.5% and 56.5%, respectively. After a median follow-up of 35 months, time to progression was 9.5 months in group A and 10.5 in group B (NS) while overall median survival was 17.5 and 17 months respectively (NS). The 2-year survival was 36% in group A and 29% in group B (NS) and the 3-year survival 22% and 13%, respectively (NS). The distant relapse rate was 38% in group A and 61% in group B (P = 0.046). Severe grade 3 4 anemia was recorded in 19% of group A and 12.5% of group B (NS), while severe leucopenia was recorded in 35.5% and 20.5% (P = 0.09) and neutropenic fever in 5% and 2.5% (NS), respectively. Severe thrombocytopenia did not differ significantly between the two treatment groups being 21.5% and 23%, respectively. Severe grade 2-3 esophageal toxicity was 19% in group A and 23% in group B (NS), while grade 3 lung toxicity was 5% and 7.5% (NS), respectively. No toxicity-related deaths were recorded.
                Concurrent administration of HTRT with carboplatin etoposide is associated with a high response and survival rate. Although a trend for higher response rate was recorded in the group of patients who received late HTRT, the overall median, 2-year and 3-year survival rates did not differ significantly between the two treatment groups. The toxicity of this promising therapeutic approach was acceptable. Comparative phase III studies with an adequate number of patients are recommended in order to answer this question. The Goldie-Coldman model explaining the kinetics of tumor cell kill and drug resistance has a potential application in designing chemotherapy regimes. In this Southwest Oncology Group (SWOG) trial we tested the alternation of two potentially noncrossresistant drug combinations with a concurrent drug combination in patients with limited small-cell lung cancer. The concurrent drug combination consisted of etoposide (VP-16), 75 mg/m2/intravenously (IV), days 1, 2, and 3; vincristine, 1.0 mg/m2/IV, days 1 and 8; Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), 40 mg/m2/IV, day 1; and cyclophosphamide, 750 mg/m2/IV, day 1 (EVAC). The alternating combination consisted of VP-16, 100 mg/m2/IV, days 1, 2, and 3; and cisplatin (CDDP), 100 mg/m2/IV, day 1, alternating with vincristine, 1.0 mg/m2/IV, days 1 and 8; Adriamycin, 50 mg/m2/IV, day 1; and cyclophosphamide, 750 mg/m2/IV, day 1 (VP-16/CDDP-VAC). Chemotherapy was administered at 3-week intervals for six cycles both before and after chest (5,000 rads/5 weeks) and whole brain radiotherapy (3,000 rads/2 weeks). One hundred ninety-nine patients received EVAC and 201 received the alternating combination. There was no significant difference in the response rate to the initial six cycles of treatment with EVAC (CR, 40%) versus the alternating combination (CR, 38%). There was no significant difference between the best response, EVAC (CR, 48%) and VP-16/CDDP-VAC (CR, 51%). Median survival for all randomized patients on EVAC is 15.1 months versus 16.5 months on the alternating combination (P = .58). Toxicities consisted primarily of bone marrow suppression, anorexia, nausea and vomiting, peripheral neuropathies, and alopecia. As in previous trials, the chest was the most common site of relapse (33%). There were no differences in the incidence and sites of relapse between the two treatment arms. These treatments appear equally effective at inducing remission and prolonging survival in patients with small-cell lung cancer. Pilot study, examining the cardioprotective effect of an antioxidant regimen in patients with malignancies receiving high dose chemo- or radiotherapy.
                14 patients with chemotherapy and 10 patients with radiotherapy were randomized in a double-blind fashion (placebo versus vitamin E and C and N-acetylcysteine). Systolic and diastolic echocardiographic parameters were determined before and within three weeks of treatment completion.
                Left ventricular ejection fraction fell significantly in patients receiving placebo (radiotherapy: 67 +/- 6 to 56 +/- 2%, p = 0.008, chemotherapy: 67 +/- 7 to 60 +/- 8%, p = 0.05). Patients on antioxidants showed no significant fall in EF (radiotherapy: 63 +/- 8 to 61 +/- 7%, chemotherapy: 67 +/- 5 to 64 +/- 6%).
                The small number of patients in the study precludes a definitive statement. The preliminary results, however, suggest efficient cardioprotection by this cheap and safe antioxidant combination, so that larger studies are warranted for confirmation. To compare the outcome of treatment of mediastinoscopy-verified N2 non-small-cell lung cancer treated with induction chemotherapy followed by either surgery or radiotherapy (RT), with both options followed by consolidation chemotherapy.
                A randomized Phase III trial for Stage IIIA (T1-T3N2M0) non-small cell lung cancer was conducted by the Radiation Therapy Oncology Group (RTOG) and Eastern Cooperative Oncology Group between April 1990 and April 1994. After documentation of N2 disease by mediastinoscopy or anterior mediastinotomy, patients received induction chemotherapy with cisplatin, vinblastine, and mitomycin-C. Mitomycin-C was later dropped from the induction regimen. Patients were then randomized to surgery or RT (64 Gy in 7 weeks) followed by cisplatin and vinblastine.
                RTOG 89-01 accrued 75 patients, of whom 73 were eligible and analyzable. Twelve patients received induction chemotherapy but were not randomized to RT or surgery thereafter. Forty-five patients were randomized to postinduction RT or surgery. Of the analyzable patients, 90% had a Karnofsky performance score of 90-100, 18% had weight loss >5%, 37% had squamous cell histologic features, and 54% had bulky N2 disease. The distribution of bulky N2 disease was uniform among the treatment arms. The incidence of Grade 4 toxicity was 56% in patients receiving mitomycin-C and 29% in those who did not. Only 1 patient in each group had acute nonhematologic toxicity greater than Grade 3 (nausea and vomiting). No acute Grade 4 radiation toxicity developed. The incidences of long-term toxicity were equivalent across the arms. Three treatment-related deaths occurred: 2 patients in the surgical arms (one late pulmonary toxicity and one pulmonary embolus), and 1 patient in the radiation arm (radiation pneumonitis). Induction chemotherapy was completed in 78% of the patients. Complete resection was performed in 73% of 26 patients undergoing thoracotomy. Consolidation chemotherapy was completed in 75% of the patients. No statistically significant difference was found among the treatment arms. The overall progression-free survival rate was 53% at 1 year and 17% at 3 years. The median progression-free survival was 14 months. No difference in the 1-year survival rate (70% vs. 66%) or median survival time (19.4 vs. 17.4 months) between the surgery and RT arms. The median survival in the patients receiving induction chemotherapy only was 8.9 months. Mitomycin-C had no impact on survival (p = 0.75). No statistically significant difference was noted in the time to local failure between the surgical and RT arms.
                The patient accrual to this trial made its results inconclusive, but several observations are notable. In this trial, histologic confirmation of N2 disease in the surgical and nonsurgical arms eliminated the usual biases from clinical staging. In this setting, local control and survival were essentially equal between the surgical and RT arms. The 3- and 5-year survival rates of nonsurgical therapy were comparable to published surgical trials of N2 disease. A clinical review with analysis of prognostic factors, including the impact of the initial management modality, was conducted on 137 patients with superior vena cava syndrome (SVCS) seen at the Veterans General Hospital-Taipei between 1989 and 1993. Malignant diseases account for most of the SVCS in our Chinese patients. Patients received diagnostic intervention for their underlying diseases without obvious complications. Whether or not there is a development of SVCS in lung cancer patients, showed prognostic significance in non-small cell lung cancer (NSCLC) and no significance in small cell lung cancer (SCLC). Those with SVCS as the initial manifestation of malignant disease had a poor prognosis compared to those who developed SVCS later. Survival is best in lymphoma/leukemia patients, followed by malignant thymoma and SCLC, and worst in NSCLC and metastatic cancer. The rapid onset of symptoms from SVCS had a short median survival in lung cancer and significantly compromised survival in SCLC. The overall survival of SCLC with SVCS was not affected, regardless of whether the initial therapy had been radiotherapy or chemotherapy. Patients with small cell lung cancer (SCLC) and superior vena cava syndrome (SVCS) are widely believed to have a grave prognosis. The purpose of this study was to determine the prognosis of patients with SCLC and SVCS as compared to SCLC without SVCS.
                A retrospective analysis of 408 cases of SCLC +/- SVCS was performed. Three- hundred and sixty showed no clinical signs of SVCS and 43 (11%) had SVCS; in 5 patients no adequate information was available about clinical signs of SVCS. All patients were classified as limited disease cases. About 98% received chemotherapy usually as the first treatment followed by radiotherapy. A median total dose of 46 Gy (range 30 to 70 Gy) was given at 2.0 Gy per fraction five times weekly. A prophylactic cranial irradiation was applied if a complete remission was achieved after chemotherapy or after 30 Gy of irradiation. Kaplan-Meier survival curves are shown and comparisons were made by the log-rank and the Gehan/Wilcoxon test. To adjust for prognostic factors, a proportional hazards analysis was done.
                Patients without SVCS had 5-year survival rates ( +/- SE) and a median survival time (MST; 95% confidence intervals) of 11% +/- 2% and 13.7 months (12.7-14.5) in UICC Stage I to III; in Stage III the figures were 9% +/- 2% and 12.6 months (11.2-13.7). In comparison, SCLC with SVCS had 5-year survival rates of 15% +/- 7% and MST of 16.1 months (13.8-20.5). The difference was significant in univariate analysis (Stage II disease: p = 0.008 by the log-rank test). In a multivariate analysis of all patients, Stage (Stage I + II > III; p = 0.0003), SVCS (yes > no; p = 0.005), and Karnofsky performance status ( < or = 70 < 80-100%; p = 0.008) were of significant importance.
                SVCS is a favorable prognostic sign in SCLC. The treatment should be curatively intended. Despite technical improvements that have minimized the morbidity and mortality of hepatic surgery, the long-term outcome of resection of hepatic metastases of colorectal cancer remains poor, with the majority of patients experiencing treatment failure in the liver. Because arterial chemotherapy regimens targeted to the liver have demonstrated high response rates, an intergroup trial of adjuvant therapy for patients undergoing hepatic resection of liver metastases from colorectal cancer was initiated.
                Patients with one to three potentially resectable metastases were randomized preoperatively to receive no further therapy (control arm, 56 patients) or postoperative hepatic arterial floxuridine combined with intravenous continuous-infusion fluorouracil (chemotherapy arm, 53 patients). After exclusion of patients identified as ineligible for the planned treatment at the time of surgery, there were 45 control patients and 30 on the chemotherapy arm. The study was powered to evaluate improvement in time to recurrence and hepatic disease-free survival, not overall survival.
                The 4-year recurrence-free rate was 25% for the control arm and 46% for the chemotherapy group (P =.04). The 4-year liver recurrence-free rate was 43% in the control group and 67% in the chemotherapy group (P =.03). The median survival of the 75 assessable patients was 49 months for the control arm and 63.7 months for the chemotherapy arm (P =.60). The median survival of all 109 patients was 47 months for the control arm compared with 34 months for the chemotherapy arm (P =.19)
                These data demonstrate that adjuvant intra-arterial and intravenous chemotherapy was beneficial in prolonging time to recurrence and pre-venting hepatic recurrence after hepatic resection of colorectal cancer. We investigated a phase III randomized trial to compare efficacy and tolerance of CDDP + 5-FU to CDDP + VP16, both given intravenously in patients with unresectable advanced head and neck cancer. The 197 eligible patients were paired off successively on the basis of tumor sites and UICC stage. Comparisons were made through sequential closed plans. In 179 patients, tumor beds and cervical lymph nodes were irradiated, and 20 patients underwent salvage surgical procedures. Cisplatin plus 5-fluorouracil showed a response (CR + PR) rate of 15% greater than that observed with cisplatin plus etoposide (alpha=0.05, power 70%). Complete responses played a major role in the CDDP + 5-FU regimen. Furthermore, we noted a higher cervical node regression with this chemotherapy combination. Because radiotherapy was administered after chemotherapy, we could not analyze the mean duration response for each protocol. No significant difference in survival existed between the two groups. Myelosuppression was the most frequent sign of toxicity observed, especially with the CDDP + VP16 regimen. Mucositis was rare with allopurinol protection. In the CDDP + 5-FU group, one patient had grade 4 cardiac dysfunction, and 3 patients exhibited unconsciousness that may be related to cerebral vascular damage. Thirteen patients died, with 8 cases related to septic shock (5 CPPP + VP16 and 3 CDDP + 5-FU). Cisplatin plus 5-FU chemotherapy showed a satisfactory efficacy and acceptable toxicity profile compared with CDDP + VP16, with caution to patients with a cardiac or vascular history. Although we could not show a benefit in survival with the CDDP + 5-FU protocol, this trial supports literature data and confirms that this regimen may be proposed as a first-line therapy in advanced cancer of the head and neck. A prospective randomized phase III trial was carried out at Songklanagarind Hospital from August 1988 to December 1990. The objectives of the study were to evaluate the effect of chemotherapy regimen in squamous cell carcinoma of the esophagus and to determine whether induction chemotherapy improves symptom-free period and survival in these patients compared to surgical treatment alone. Twenty-four patients were randomized to receive 2 cycles of chemotherapy, cis-platinum 100 mg/m2 intravenously on day 1, bleomycin 10 mg/m2 loading dose on day 3, followed by 10 mg/m2/day continuous intravenous infusion on days 4 through 7, and vinblastine 3 mg/m2 given intravenously on days 1, 8, 15, 22. The cycle was repeated on day 29. Fifteen patients completed 2 courses of chemotherapy and among these, 2 patients had a complete clinical response (13%), 6 (40%) had a partial response, and 7 patients (47%) had no response. Four patients died during chemotherapy treatment. Grade 3 hematologic toxicity (ECOG criteria) was observed in 47% (7/15) of patients. Twenty-two patients were randomized to conventional treatment (surgery alone). Median survival time was 17 months in both groups. However, early survival appeared to be better in the control group. Kaplan-Meier survivals at 6 months were 69% and 89% and at 3 years were 31% and 36% for the induction chemotherapy group and control group, respectively. The survival time differences were not statistically significant (P = 0.186). These findings demonstrate that although this chemotherapy regimen had some effect on squamous cell carcinoma of esophagus, it did not improve survival. On the contrary, survival seems to be better in the control group. The 6-month survival discrepancy between both groups might be due to the poor nutritional status of our patients, who may better tolerate smaller dosages of chemotherapy. In a randomised prospective trial of chemotherapy with and without radiotherapy in small-cell carcinoma of the bronchus, 37 of 366 patients presented with obstruction of the superior vena cava at the time of diagnosis. In the study all patients received four cycles of combination chemotherapy over a period of 12 weeks and, provided there was not progressive disease, then received either radiotherapy to the mediastinum and primary tumour followed by eight further courses of chemotherapy or eight cycles of chemotherapy alone. Of the 37 patients presenting with superior vena caval obstruction, nine had relapsed and treatment was stopped during or after the initial four cycles of chemotherapy. Of the remainder, 15 patients received radiotherapy plus chemotherapy and 13 chemotherapy alone. After four cycles of chemotherapy (12 weeks) 21 of the 37 patients had initial complete relief of symptoms secondary to superior vena caval obstruction, 10 had substantial but partial relief, and six had no relief. Twelve patients developed recurrence of superior vena caval obstruction, of whom six had received radiotherapy and four chemotherapy alone; two relapsed in the initial 12 weeks of the study. The median survival of the patients with superior vena caval obstruction allocated at diagnosis to either treatment arm was identical. The survival of patients with obstruction was similar to that of other patients in the main study. Chemotherapy is an effective treatment for superior vena caval obstruction and there appears to be no additional advantage in giving radiotherapy after 12 weeks of cyclical chemotherapy. To demonstrate the efficacy of radiochemotherapy (RCT) as the first choice of treatment for advanced unresectable head-and-neck cancer. To prove an expected benefit of simultaneously given chemotherapy, a two-arm randomized study with hyperfractionated accelerated radiochemotherapy (HF-ACC-RCT) vs. hyperfractionated accelerated radiotherapy (HF-ACC-RT) was initiated. The primary endpoint was 1-year survival with local control (SLC).
                Patients with Stage III and IV (UICC) unresectable oro- and hypopharyngeal carcinomas were randomized for HF-ACC-RCT with 2 cycles of 5-FU (600 mg/m(2)/day)/carboplatinum (70 mg/m(2)) on days 1--5 and 29--33 (arm A) or HF-ACC-RT alone (arm B). In both arms, there was a second randomization for testing the effect of prophylactically given G-CSF (263 microg, days 15--19) on mucosal toxicity. Total RT dose in both arms was 69.9 Gy in 38 days, with a concomitant boost regimen (weeks 1--3: 1.8 Gy/day, weeks 4 and 5: b.i.d. RT with 1.8 Gy/1.5 Gy). Between July 1995 and May 1999, 263 patients were randomized (median age 56 years; 96% Stage IV tumors, 4% Stage III tumors).
                This analysis is based on 240 patients: 113 patients with RCT and 127 patients with RT, qualified for protocol and starting treatment. There were 178 oropharyngeal and 62 hypopharyngeal carcinomas. Treatment was tolerable in both arms, with a higher mucosal toxicity after RCT. Restaging showed comparable nonsignificant different CR + PR rates of 92.4% after RCT and 87.9% after RT (p = 0.29). After a median observed time of 22.3 months, l- and 2-year local-regional control (LRC) rates were 69% and 51% after RCT and 58% and 45% after RT (p = 0.14). There was a significantly better 1-year SLC after RCT (58%) compared with RT (44%, p = 0.05). Patients with oropharyngeal carcinomas showed significantly better SLC after RCT (60%) vs. RT (40%, p = 0.01); the smaller group of hypopharyngeal carcinomas had no statistical benefit of RCT (p = 0.84). For both tumor locations, prophylactically given G-CSF was a poor prognostic factor (Cox regression), and resulted in reduced LRC (log-rank test: +/- G-CSF, p = 0.0072).
                With accelerated radiotherapy, the efficiency of simultaneously given chemotherapy may be not as high as expected when compared to standard fractionated RT. Oropharyngeal carcinomas showed better LRC after HF-ACC-RCT vs. HF-ACC-RT; hypopharyngeal carcinomas did not. Prophylactic G-CSF resulted in an unexpected reduced local control and should be given in radiotherapy regimen only with strong hematologic indication. Expandable metallic stents were successfully introduced in 12 patients; 6 with superior vena cava (SVC) obstruction due to tumor invasion or lymph node metastases, 3 with inferior vena cava (IVC) obstruction or stenosis due to lymph node metastases or hepatic tumor, one with common iliac vein (CIV) obstruction due to lymph node metastases, one with idiopathic obstruction of the hepatic IVC and Budd-Chiari syndrome, and one with CIV obstruction following a dialysis shunt. The length of the lesions was between 2 and 15 cm. Multiple (2-7) stents in tandem were inserted percutaneously from a femoral venous approach through a 12 to 16 F (4.0-5.3 mm) Teflon sheath. Postoperatively, all 12 patients became free from symptoms such as SVC syndrome or IVC syndrome. In 11 patients, the symptoms did not recur during the follow-up periods of 1 to 21 months. Between January 1989 and December 1991, 64 patients with advanced cervical carcinoma FIGO stage IIb-III were randomized to receive radiotherapy (RT) alone or the sequential combination of chemotherapy (CT) and RT. RT consisted of external RT (40 Gy fractionated over 4 weeks)+brachy-therapy (40 Gy to point A)+an additional boost to the parameters (15-20 Gy) in arm RT; CT consisted of cisplatin 60 mg/m2 i.v. day 1 q 15 days administered for 2 cycles before the start of RT and for 4 cycles after the end of radiation treatment in CT+RT arm. Among the 58 evaluable patients objective response rate was as follows: in RT arm, CR in 40.7% of patients, PR in 40.7%, and SD in 18.6%; in CT+RT arm, CR in 42% of patients, PR in 35.5%, and SD in 22.5%. The median duration of response was 12 months (range: 3-38 + months). At a median follow-up of 36 months survival (S) and progression-free survival (PFS) were 83% and 72.4% in RT arm, 72% and 59.3% in CT+RT arm, respectively. No significant difference was observed between the 2 treatment arms, neither in terms of objective response nor in terms of S and PFS. Both treatments were generally well tolerated. In our experience the addition of chemotherapy to standard radiotherapy does not enhance morbidity and does not interfere with the correct delivery of the planned treatment. However, results of this combined modality regimen remain unsatisfactory, since no improvement in pelvic control and survival of patients with advanced cervical carcinoma was observed. The purpose of this study was to determine the feasibility of using Wallstent implantation to treat superior vena cava syndrome due to malignant tumors.
                Digital subtraction angiography showed obstruction of the superior vena cava in 13 patients who then underwent transluminal dilatation and Wallstent implantation. The patients were treated with IV heparin and monitored in the emergency department. Thereafter, they were treated with a platelet inhibitor for 4 weeks.
                Because their signs and symptoms improved, patients were able to resume radiation therapy, chemotherapy, or both. One patient died of cardiac arrhythmia 1 day after stent placement. Although eight patients have subsequently died of their bronchial or thyroid gland tumors, superior vena cava syndrome did not recur in any patient.
                Percutaneous implantation of Wallstent endoprostheses provides excellent palliation for superior vena cava syndrome. In a prospective multicenter study, 186 patients with squamous cell esophageal carcinoma, who after evaluation were considered suitable for surgery, were randomized to 4 treatment groups: Group 1, surgery alone; Group 2, pre-operative chemotherapy (cisplatin and bleomycin) and surgery; Group 3, pre-operative irradiation (35 Gy) and surgery; Group 4, pre-operative chemotherapy, radiotherapy, and surgery. Three-year survival was significantly higher in the pooled groups receiving radiotherapy as compared with the pooled groups not receiving radiotherapy. Comparison of the groups having pre-operative chemotherapy with those not having chemotherapy showed no significant difference in survival. Female patients had a significantly better survival than males. The results indicate that pre-operative irradiation had a beneficial effect on intermediate term survival, whereas the chemotherapy regime used did not influence survival. Between 1983 and 1986, the National Institute for Cancer Research in Genoa and affiliated institutions conducted a randomized study to compare two different ways of combining chemotherapy (CT) and radiation therapy (RT). One hundred sixteen patients were randomized to receive neoadjuvant CT followed by definitive RT (treatment arm A) or alternating CT and RT. In treatment arm A, RT consisted of 70 Gy to the involved areas and 50 Gy to the uninvolved neck at 2 Gy/fraction, five fractions per week. In treatment arm B, RT consisted of 60 Gy to involved areas and 50 Gy to the uninvolved neck in three courses of 20 Gy each, 2 Gy/fraction, ten fractions/2 weeks alternated with four courses of CT. CT consisted of vinblastine 6 mg/m2 intravenously followed 6 hours later by bleomycin 30 IU intramuscularly, day 1; methotrexate 200 mg intravenously, day 2; leucovorin rescue, day 3. CT was repeated every 2 weeks up to four courses. The same CT was used in both treatment arms of the study. Fifty-five patients were entered in treatment arm A and 61 in treatment arm B. Complete responses were 7/48 and 19/57 in treatment arms A and B, respectively (P less than 0.03). Four-year progression-free survival was 4% in treatment arm A and 12% in treatment arm B (P less than 0.02), and four-year survival was 10% in A and 22% in B (P less than 0.02). Mucosal tolerance was significantly worse in treatment arm B (P less than 0.00004). The subgroup analysis shows the major improvement of alternating CT and RT in patients with the worst prognostic characteristics. The incidence, response to chemotherapy treatment and prognostic value in the prediction of the Superior Cave vein syndrome (SVCS) surveillance were retrospectively studied in a group of 125 patients presenting microcytic pulmonary carcinoma. We found SVCS in 20 cases (16% of the total group of patients), there were no statistically significant differences between the limited or diseminated stages. All patients were initially treated with polychemotherapy. The efficacy of this treatment to eliminate the symptoms of SVCS could be evaluated in 17 cases while in the other 3 cases that was not possible give the early or toxic death of the patients. Fourteen out of the 17 patients with evaluable SVCS (82%) achieved a complete remission of the syndrome with chemotherapy which parallel with the achievement of a partial or complete response of the primary tumor and its metastasis. The SVCS only reappeared in one case at the moment of tumor recurrence. The remission of symptoms was quickly initiated after treatment and was completed in most cases one week after treatment was started. An statistically significant difference was not observed between the surveillance of patients who presented SVCS at time of diagnosis and those who did not. Given that both groups were balanced with regard to the rest of the prognostic factors (the disease stage, Karnofsky's index, sex, or treatment) the SVCS does not constitute a pejorative prognostic factor in the prediction of surveillance in microcytic pulmonary carcinoma. To compare the survival of patients with medically inoperable or unresectable stage III non-small cell lung cancer treated with thoracic radiotherapy alone or in combination with chemotherapy.
                Randomized, prospective phase III trial.
                Multi-institutional cooperative oncology group.
                A total of 121 patients were enrolled in the study, of whom 7 (5.8%) were ineligible. All patients were ambulatory and had measurable or evaluable disease. Before they were randomized, patients were stratified by ECOG performance score, histologic type, maximum tumor diameter, and NCCTG institution.
                Radiotherapy consisted of a total of 5000 cGy in 5 weeks with a 1000 cGy boost in 5 fractions to a small tumor field. Combined modality therapy was MACC which is intravenous methotrexate, intravenous doxorubicin, intravenous cyclophosphamide, and oral lomustine (CCNU), on day 1 and 28. Chemotherapy was followed by identical thoracic radiotherapy 4 weeks after the second cycle of chemotherapy. Four weeks after thoracic radiotherapy was completed, patients received another two cycles of identical chemotherapy. Patients who had progression of disease after chest irradiation only were treated with MACC chemotherapy.
                Major clinical responses were observed in 31 of 56 (55%; 95% Cl, 42% to 68%) patients treated with combination therapy and 37 of 58 (64%; Cl, 51% to 76%) treated with radiation only (P greater than 0.2). The median time to progression was 192 days with radiotherapy only compared with 199 days for combined modality therapy (P greater than 0.2). The median survival time was 313 days compared with 317 days, respectively (P greater than 0.2). The 1-, 2-, and 5-year survival rates after thoracic radiation only were 45% (Cl, 32% to 58%), 16% (Cl, 6% to 25%), and 7%. With chemoradiotherapy, the survival rates were 46% (Cl, 33% to 60%), 21% (Cl, 11% to 32%), and 5%, respectively. Myelosuppression was significantly greater for the combined modality therapy arm (P = 0.002).
                Chemotherapy with MACC, in combination with thoracic radiotherapy, did not result in significant survival advantage compared with radiation alone (P greater than 0.2) in patients with medically inoperable or unresectable stage III non-small cell lung cancer. Between 1975 and 1978, 23 patients with Stage IV, unresectable, squamous cell carcinoma of the head and neck were randomized to receive radiotherapy (RT, 11 patients), or radiotherapy-chemotherapy (RT & CT, 12 patients). The response rate for the 12 RT & CT patients was four complete remissions (CR) and four partial remissions (PR); the 11 RT patients had one CR and three PR. The presence of a responses (CR or PR) significantly enhanced the median survival (14 vs. 5 months; P = 0.005). The duration of objectives remission was longer among the RT & CT patients when compared with RT patients (6 vs. 2.3 months, P = 0.18). The median survival of the RT & CT group was 12 months compared with 5.6 months for the RT group (P = 0.13). One RT & CT patient remains alive with disease at 44 months, one RT patient remains alive without disease at 30 months. The present chemotherapy regimen did not modify the pattern of failure and only marginally increased patient survival. It did, however, increase the response rate. The authors plan to reactivate the trial with modification in the induction chemotherapy and the addition of postradiation maintenance CT consisting of sequential bleomycin and cis-platinum.
Chemotherapy and radiotherapy are effective in relieving SVCO in a proportion of patients whereas stent insertion appears to provide relief in a higher proportion and more rapidly. The optimal timing of stent insertion (whether at diagnosis or following failure of other modalities) and the effectiveness of steroids remain uncertain.