Extended-field radiotherapy is superior to MOPP chemotherapy for the treatment of pathologic stage I-IIA Hodgkin's disease: eight-year update of an Italian prospective randomized study. Prospective, multicenter randomized GITMO/IIL trial comparing intensive (R-HDS) versus conventional (CHOP-R) chemoimmunotherapy in high-risk follicular lymphoma at diagnosis: the superior disease control of R-HDS does not translate into an overall survival advantage. Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial. Concurrent and adjuvant chemotherapy for nasopharyngeal carcinoma: a factorial study. Initial versus delayed accelerated hyperfractionated radiation therapy and concurrent chemotherapy in limited small-cell lung cancer: a randomized study. Results of a prospective randomized clinical trial of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by radiation therapy (RT) versus ABVD alone for stages I, II, and IIIA nonbulky Hodgkin disease. Randomized phase III trial of sequential adjuvant chemoradiotherapy with or without erythropoietin Alfa in patients with high-risk cervical cancer: results of the NOGGO-AGO intergroup study. Randomized trial of hyperfractionated radiation therapy with or without concurrent chemotherapy for stage III non-small-cell lung cancer. Chemotherapy of Hodgkin's lymphoma with alternating cycles of COPP (cyclophosphamide, vincristin, procarbazine, prednisone) and ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine). Results of the HD1 and HD3 trials of the German Hodgkin Study Group. A randomised study of adjuvant MVPP chemotherapy after mantle radiotherapy in pathologically staged IA-IIB Hodgkin's disease: 10-year follow-up. Radiation therapy alone or with concurrent low-dose daily either cisplatin or carboplatin in locally advanced unresectable squamous cell carcinoma of the head and neck: a prospective randomized trial. Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin's lymphoma: final analysis of the prospective LNH87-2 protocol--a groupe d'Etude des lymphomes de l'Adulte study. Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy--results of a multicentric randomized German trial in advanced head-and-neck cancer. Treatment of locally advanced squamous-cell carcinoma of the head and neck with concurrent radiochemotherapy - randomized comparison of Cisplatin versus Carboplatin. Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: a prospective randomized trial. Patients with stage III/IV Hodgkin's disease in partial remission after MOPP/ABV chemotherapy have excellent prognosis after additional involved-field radiotherapy: interim results from the ongoing EORTC-LCG and GPMC phase III trial. The EORTC Lymphoma Cooperative Group and Groupe Pierre-et-Marie-Curie. A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Pelvic irradiation with concurrent chemotherapy versus pelvic and para-aortic irradiation for high-risk cervical cancer: an update of radiation therapy oncology group trial (RTOG) 90-01. Treatment of children with metastatic soft tissue sarcoma with oral maintenance compared to high dose chemotherapy: report of the HD CWS-96 trial.
To compare the effectiveness of chemotherapy (CHT) with extended-field radiotherapy (RT) in the treatment of early-stage Hodgkin's disease (ESHD), we report an 8-year updated analysis of a study in which treatment with six cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) CHT was randomly compared with extended-field RT.
                From August 1979 to December 1982, 89 adult patients with pathologic stage I-IIA Hodgkin's disease (HD) were randomly allocated to receive either RT with mantle field followed by periaortic irradiation (n = 45) or six monthly courses of MOPP CHT (n = 44).
                All patients in the RT arm and 40 of 44 in the CHT arm achieved complete remission. Twelve relapses occurred in each group. Eight patients treated with MOPP and two of the RT arm died of HD. Three other patients of the CHT group died because of a second cancer. With a median follow-up greater than 8 years, the overall survival rate is significantly higher in the RT than in the CHT group (93% v 56%; P less than .001), whereas the rates of freedom from progression and relapse-free survival (RFS) were similar in the two groups (76% v 64% and 70% v 71%, respectively). Of the 12 patients relapsing after RT, 11 (92%) achieved a second CR, compared with only six of the 12 (50%) in the MOPP group. Analysis of the response rate to salvage treatments showed that the type of relapse in the MOPP group was a prognostic indicator for the achievement of a second CR, whereas in the RT group, a second CR was obtained regardless of the characteristics of the relapses. At 80 months, the probability of survival of relapsing patients calculated from time of relapse was 85% and 15% in the RT and CHT groups, respectively (P = .02).
                We conclude that RT alone is the treatment of choice for adult patients with ESHD with favorable prognostic factors. In this randomized multicenter study of 136 patients, 6 courses of CHOP (cyclo-phosphamide/doxorubicin/vincristine/prednisone) followed by rituximab (CHOP-R) were compared with rituximab-supplemented high-dose sequential chemotherapy with autografting (R-HDS) to assess the value of intensified chemo-therapy as a first-line treatment for high-risk follicular lymphoma (FL) after the introduction of monoclonal antibodies. The analysis was intention to treat with event-free survival (EFS) as the primary endpoint. Complete remission (CR) was 62% with CHOP-R and 85% with R-HDS (P < .001). At a median follow-up (MFU) of 51 months, the 4-year EFS was 28% and 61%, respectively (P < .001), with no difference in overall survival (OS). Molecular remission (MR) was achieved in 44% of CHOP-R and 80% of R-HDS patients (P < .001), and was the strongest independent outcome predictor. Patients relapsing after CHOP-R underwent salvage R-HDS in 71% of cases. Salvage R-HDS had an 85% CR rate and a 68% 3-year EFS (MFU, 30 months). We conclude that (1) achieving MR is critical for effective disease control, regardless of which treatment is used; (2) R-HDS ensures superior disease control and molecular outcome than CHOP-R, but no OS improvement; and (3) CHOP-R failures have a good outcome after salvage R-HDS, suggesting that relapsed/refractory FL could be the most appropriate setting for R-HDS-like treatments. This trial was registered at www.clinicaltrials.gov as no. NCT00435955. Nasopharyngeal carcinoma (NPC) is highly sensitive to both radiotherapy (RT) and chemotherapy. This randomized phase III trial compared concurrent cisplatin-RT (CRT) with RT alone in patients with locoregionally advanced NPC.
                Patients with Ho's N2 or N3 stage or N1 stage with nodal size > or = 4 cm were randomized to receive cisplatin 40 mg/m(2) weekly up to 8 weeks concurrently with radical RT (CRT) or RT alone. The primary end point was progression-free survival (PFS).
                Three hundred fifty eligible patients were randomized. Baseline patient characteristics were comparable in both arms. There were significantly more toxicities, including mucositis, myelosuppression, and weight loss in the CRT arm. There were no treatment-related deaths in the CRT arm, and one patient died during treatment in the RT-alone arm. At a median follow-up of 2.71 years, the 2-year PFS was 76% in the CRT arm and 69% in the RT-alone arm (P =.10) with a hazards ratio of 1.367 (95% confidence interval [CI], 0.93 to 2.00). The treatment effect had a significant covariate interaction with tumor stage, and a subgroup analysis demonstrated a highly significant difference in favor of the CRT arm in Ho's stage T3 (P =.0075) with a hazards ratio of 2.328 (95% CI, 1.26 to 4.28). For T3 stage, the time to first distant failure was statistically significantly different in favor of the CRT arm (P =.016).
                Concurrent CRT is well tolerated in patients with advanced NPC in endemic areas. Although PFS was not significantly different between the concurrent CRT arm and the RT-alone arm in the overall comparison, PFS was significantly prolonged in patients with advanced tumor and node stages. To study the efficacy of concurrent chemoradiotherapy (CRT) and adjuvant chemotherapy (AC) for nasopharyngeal carcinoma (NPC).
                Patients with Ho's stage T3 or N2/N3 NPC or neck node > or = 4 cm were eligible. Patients were randomly assigned to have radiotherapy (RT) or CRT with uracil and tegafur and to have AC or no AC after RT/CRT. AC comprised alternating cisplatin, fluorouracil, vincristine, bleomycin, and methotrexate for six cycles. There were four treatment groups: A, RT; B, CRT; C, RT and AC; D, CRT and AC. For CRT versus RT, groups B and D were compared with groups A and C. For AC versus no AC, groups C and D were compared with groups A and B.
                Three-year failure-free survival (FFS) and overall survival (OS) for CRT versus RT were 69.3% versus 57.8% and 86.5% versus 76.8%, respectively (P =.14 and.06; n = 110 v 109). Distant metastases rate (DMR) was significantly reduced with CRT (14.8% v 29.4%; P =.026). Locoregional failure rates (LRFR) were similar (20% v 27.6%; P =.39). Three-year FFS and OS for AC versus no AC were 62.5% versus 65% and 80.4% versus 83.1%, respectively (P =.83 and.69; n = 111 v 108). DMR and LRFR were not reduced with AC (P =.34 and.15, respectively). Cox model showed CRT to be a favorable prognostic factor for OS (hazard ratio, 0.42; P =.009).
                An improvement in OS with CRT was observed but did not achieve statistical significance. The improvement seemed to be associated with a significant reduction in DMR. AC did not improve outcome. To perform a randomized study of the optimal timing of thoracic radiation (RT) as accelerated hyperfractionated radiation therapy (ACC HFX RT) in combination with concurrent chemotherapy (CHT) in limited-stage small-cell lung cancer (SCLC).
                Between 1988 and 1992, 107 patients were enrolled and 103 were assessable. All patients received ACC HFX RT with 1.5 Gy twice daily to 54 Gy plus concurrent daily carboplatin/etoposide (C/E) (30 mg each) and four sequential cycles of cisplatin/etoposide (PE) (30 mg/m2 and 120 mg/m2, respectively, on days 1 to 3). Group I patients (n = 52) received concurrent chemoradiation at weeks 1 to 4, and group II (n = 51) at weeks 6 to 9. Patients who showed a complete response (CR) or partial response (PR) underwent prophylactic cranial irradiation (PCI) at weeks 16 to 17.
                The median survival time was 34 months in group I and 26 months in group II, and the Kaplan-Meier 5-year survival rates were 30% and 15%, respectively. The difference was almost significant on univariate analysis (P = .052) and was significant on multivariate analysis (P = .027). Group I patients had a significantly higher local control rate than group II patients, but there was no difference between the two groups in distant metastasis rate. There was no difference in the incidence of acute or late grade 3 to 4 toxicity.
                Initial administration of thoracic ACC HFX RT with concurrent C/E seems to produce better local control and survival rates than delayed administration. To determine whether combined modality therapy (CMT) is superior to chemotherapy (CT) alone, 152 untreated Hodgkin disease patients with clinical stages (CSs) IA, IB, IIA, IIB, and IIIA without bulk disease were prospectively randomized to 6 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) alone or 6 cycles of ABVD followed by radiation therapy (RT) (3600 cGy: involved field for 11 patients, modified extended field for the rest). Of 76 patients randomized to receive RT, 65 actually received it, and 11 did not (4 progressed, 1 had bleomycin toxicity, 6 refused). For ABVD + RT, the complete remission (CR) percentage was 94% and no major response, 6%. For ABVD alone, 94% achieved a CR; 1.5%, a partial response (PR); and 4.5%, no major response. At 60 months CR duration, freedom from progression (FFP), and overall survival (OS) for ABVD + RT versus ABVD alone are 91% versus 87% (P = .61), 86% versus 81% (P = .61), and 97% versus 90% (P = .08), respectively (log-rank). The 95% confidence intervals for CR duration, FFP, and OS differences at 5 years were -8% to 15%, -8% to 18%, and -4% to 12%, respectively. Although significant differences were not seen, it is possible that a benefit in outcome of less than 20% for CMT might be seen in a larger trial. This open-label, randomized phase III study was designed to investigate the effects of erythropoietin alfa (EPO) in addition to adjuvant chemotherapy and pelvic radiotherapy (CRT) in patients with stage IB to II cervical cancer who had undergone radical hysterectomy.
                Two hundred fifty-seven patients were randomly assigned to four cycles of carboplatin/ifosfamide chemotherapy followed by external-beam pelvic radiotherapy (CRT group) or four cycles of carboplatin/ifosfamide chemotherapy and EPO followed by pelvic radiotherapy and EPO (CRT + EPO group). The primary end point was recurrence-free survival (RFS). Secondary end points included overall survival (OS), change in hemoglobin levels, and safety, including thromboembolic events.
                The estimated 5-year RFS rates were 78% for patients receiving CRT + EPO and 70% for patients receiving CRT. There was no statistically significant difference in RFS, although a trend favoring patients treated with CRT + EPO was observed (hazard ratio [HR], 0.66; 95% CI, 0.39 to 1.12; log-rank P = .06). Exploratory analyses suggest a benefit with CRT + EPO for patients with stage IB to IIA disease (HR, 0.39; 95% CI, 0.18 to 0.85; P = .014) or patients with complete resection (HR, 0.55; 95% CI, 0.31 to 0.98; P = .039). OS was similar in both groups (HR, 0.88; 95% CI, 0.51 to 1.50; log-rank P = .63). Patients treated with EPO maintained higher hemoglobin levels throughout CRT. No significant differences in safety profiles were observed between the two groups. Incidence of thrombovascular events was low (2%) and comparable between both groups.
                This study confirms that EPO can be added safely to CRT in patients with cervical cancer, but it failed to demonstrate a significant benefit in RFS and OS. To investigate the efficacy of combined hyperfractionated radiation therapy (HFX RT) and concurrent chemotherapy (CHT) in stage IIIA or IIIB non-small-cell lung cancer (NSCLC) compared with that of HFX RT alone.
                Between January 1988 and December 1989, 169 patients were divided randomly into the following groups: group I, HFX RT with 1.2 Gy twice daily to a total dose of 64.8 Gy (n = 61); group II, same HFX RT with CHT consisting of 100 mg of carboplatin (CBDCA) on days 1 and 2 and 100 mg of etoposide (VP-16) on days 1 to 3 of each week during the RT course (n = 52); and group III, same HFX RT with CHT consisting of 200 mg of CBDCA on days 1 and 2 and 100 mg of VP-16 on days 1 to 5 of the first, third, and fifth weeks of the RT course (n = 56).
                The median survival time (MST) was 8 months for group I, 18 months for group II, and 13 months for group III. The 3-year survival rates were 6.6%, 23%, and 16%, respectively. There was a significant difference in the survival rate between groups I and II (P = .0027, log-rank test), but not between groups I and III (P = .17) or between groups II and III (P = .14). The relapse-free survival rate in group II was also higher than that in group I (P = .0024), which was largely due to improved local control in group II patients. Patients in groups II and III showed a higher incidence of acute and/or late high-grade toxicity compared with group I patients, but no patient died of treatment-related toxicity.
                The combination of HFX RT and continuous CBDCA/VP-16 CHT was tolerable and substantially increased the survival rate. Untreated patients with Hodgkin's lymphoma in stages I-IIIA with risk factors (large mediastinal mass, massive splenic involvement, extranodal disease) were entered into the HD1 protocol and received a combined chemo-radiotherapy [2 X (COPP + ABVD) + 40 Gy extended field irradiation (EF) vs 2 X (COPP + ABVD) + 20 Gy EF]. Patients in stages IIIB/IV (HD3 protocol) received induction chemotherapy [3 X (COPP + ABVD)] and were randomized into consolidation by radiotherapy [20 Gy involved field irradiation (IF)] vs chemotherapy [1 X (COPP + ABVD)]. Seventy-three of 89 evaluable patients (82%) treated according to the HD1 protocol achieved a complete remission. Freedom from progression and survival of patients in stages I-IIIA with risk factors treated according to HD1 were no worse than those of patients in stages I and II without risk factors who received only radiotherapy. Eighty-six of 137 patients (63%) treated according to the HD3 protocol achieved complete remission after induction chemotherapy with COPP + ABVD. This is significantly better than the 31% complete remission rate observed in a previous pilot study with COPP alone (P less than 0.01). Including salvage therapy (radiotherapy in case of persisting nodal disease; chemotherapy with 4 X CEVD in case of persisting disseminated disease), a total of 76% complete remissions in stages IIIB/IVAB were achieved. A high erythrocyte sedimentation rate (greater than 80 mm h-1) was the most significant risk factor for achieving freedom from progression. One hundred fifteen untreated patients with supra-diaphragmatic, pathologically staged (PS) IA-IIB Hodgkin's disease (HD) were entered into a randomised study comparing treatment using mantle radiotherapy followed by adjuvant treatment with mustine, vinblastine, prednisolone, and procarbazine (MVPP) with mantle radiotherapy alone. Fifty-six patients were randomised to receive radiotherapy alone (RT) and 59 to radiotherapy followed by six cycles of adjuvant MVPP (RT + MVPP). One hundred fourteen patients achieved a complete remission (CR) with radiotherapy. One patient achieved a partial remission. The overall 10-year survival after correction for intercurrent death was 92% with no difference between the two treatment groups (90% for RT alone and 95% for RT + MVPP P = 0.66). There were 9 (8%) deaths from HD (5 patients had received RT alone), and 10 (9%) intercurrent deaths. Eight (7%) patients have developed a second malignancy, and two of them are alive. No patient has developed secondary acute myelogenous leukaemia. The 10-year relapse-free survival (RFS) was 79% overall, 67% in the RT group, and 91% in the RT + MVPP group (P = 0.0004). There were 25 relapses; 20 patients had received RT alone and 5 had received adjuvant MVPP. Of the relapsed patients, 13 (52%) have received successful salvage therapy and are in CR. In the RT alone group, 45 (80%) patients are alive in CR, 5 (9%) died of HD, and 6 (11%) died of intercurrent causes. In the adjuvant MVPP group, 51 (86%) are alive in CR, 4 (7%) died of HD, and 4 (7%) died of intercurrent causes.(ABSTRACT TRUNCATED AT 250 WORDS) Between January 1988 and December 1991, 159 patients with Stage III/IV (M0) squamous cell carcinoma of the head and neck were randomized to receive standard fraction RT (70 Gy) (group I) or the same RT plus either 6 mg/m2 of cisplatin (CDPP) (group II) or 25 mg/ m2 of carboplatin (CBDCA) both given daily during RT (group III). Patients in groups II and III had significantly higher overall response rates then those in group I (P = 0.011 and P = 0.0025, respectively) with no difference between groups II and III (P = 0.60). They also had significantly longer median survival time (MST) and higher 5-year survival rates than those in group I (MST, 32 months (32%) and 30 months (29%) versus 16 months (15%), respectively; P = 0.011 and P = 0.019, respectively), with no difference between the two RT/CHT groups. Median time to local recurrence (MTLR) and 5-year local recurrence-free survival (LRFS) were significantly higher for both RT/CHT when compared to RT alone (MTLR, not attained yet and 30 months versus 10 months, respectively; 5-year LRFS, 51% and 48% versus 27%, respectively; P = 0.018 and P = 0.040, respectively) with no difference between the two RT/CHT groups. There was no difference between the three treatment groups regarding regional lymph node and distant metastasis control. Apart from acute high grade (> or =3) hematological toxicity that was significantly more frequent in the two RT/CHT groups and no different between the two RT/CHT groups, other acute high grade toxicity was similar between the three treatment groups. Late high grade toxicity was infrequent and similar between the three treatment groups. To present the final analysis, with a median follow-up of 8 years, of the LNH87-2 randomized study, which compares consolidative sequential chemotherapy (ifosfamide plus etoposide, asparaginase, and cytarabine) with high-dose therapy (HDT) using cyclophosphamide, carmustine, and etoposide (CBV regimen) followed by stem-cell transplantation in patients with aggressive non-Hodgkin's lymphoma in first complete remission after induction, focusing on high/intermediate- and high-risk patients identified by the age-adjusted international prognostic index.
                Among the 916 eligible patients, 451 presented with two (n = 318) or three (n = 133) risk factors. After reaching complete remission to induction therapy, 236 of these higher risk patients were assessable for the consolidation phase, with 125 patients in the HDT arm and 111 in the sequential chemotherapy arm.
                Among these 451 higher risk patients, 277 (61%) achieved complete remission after induction treatment. In the population of 236 randomized patients, HDT was superior to sequential chemotherapy, with 8-year disease-free survival rates of 55% (95% confidence interval [CI], 46% to 64%) and 39% (95% CI, 30% to 48%), respectively (P =.02; relative risk, 1.56). The 8-year survival rate was significantly superior in the HDT arm (64%; 95% CI, 55% to 73%) compared with the sequential chemotherapy arm (49%; 95% CI, 39% to 59%) (P =.04; relative risk, 1.51).
                On the basis of the final analysis of this prospectively treated series of patients, retrospectively analyzed on the basis of the International Prognostic Index, we hypothesize that HDT benefits patients at higher risk who achieve complete remission after induction treatment. 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. Several phase II studies have shown that concurrent chemotherapy and radiotherapy (RT) improves the response rates and locoregional control in patients with advanced, unresectable squamous-cell carcinoma of the head and neck (H&N). However, it is still unclear which is the drug of choice to be given with RT. We therefore conducted a randomized comparison of cisplatin (CDDP)-RT versus carboplatin (CRP)-RT in such patients. The two platinum compounds were given at equitoxic doses. The primary objective of the study was to compare the side effects and the response rates of the two regimens. Radiotherapy was given at conventional dosages, 2 Gy for 5 days every week for a total dose of 64 Gy with CDDP 80 mg/m2 or CRP 375 mg/m2 for three cycles on days 1, 21 and 42. At present 53 patients are entered in the study: 27 in the CDDP arm and 26 in the CRP. The two arms were balanced for all the pre-treatment characteristics. Both the schedules were well tolerated. However, incidence of nausea and vomiting (p=0.0045); anemia (p=0.032) and peripheral neuropathy (p=0.032) was significantly greater with CDDP-RT as compared to CRP-RT. On the other hand, CRP-RT gives a significantly higher incidence of stomatitis (p=0.0067) and a marginally worse thrombocytopenia (p=0.09). The complete response (CR) rates were similar in the two arms (55.5% in the CDDP-RT versus 61.5% in that CRP-RT, respectively) as well as the overall response rates (92.5% versus 84.5%, respectively; p=0.36). The estimated 1 -and 2 year overall and disease-free survival rates were not significantly different in the two arms. In both the groups logistic-regression models showed that those patients with a CR (p=0.017); stage III (p=0.011); smaller primary (p=0.025) and limited node-involvement (p<0.001) had a significant better survival. We conclude that concurrent chemo-radiotherapy is an effective and safe treatment for patients with locally advanced H&N cancer. The combination CRP-RT possess a similar activity but a different, and perhaps a more favorable, spectrum of toxicity when compared to the CDDP-RT therapy. Survival results need to be assessed in a larger series and followed for a more prolonged time. To investigate whether the addition of cisplatin (CDDP) to hyperfractionation (Hfx) radiation therapy (RT) offers an advantage over the same Hfx RT given alone in locally advanced (stages III and IV) squamous cell carcinoma of the head and neck.
                One hundred thirty patients were randomized to receive either Hfx RT alone to a tumor dose of 77 Gy in 70 fractions in 35 treatment days over 7 weeks (group I, n = 65) or the same Hfx RT and concurrent low-dose (6 mg/m(2)) daily CDDP (group II, n = 65).
                Hfx RT/chemotherapy offered significantly higher survival rates than Hfx RT alone (68% v 49% at 2 years and 46% v 25% at 5 years; P =.0075). It also offered higher progression-free survival (46% v 25% at 5 years; P =.0068), higher locoregional progression-free survival (LRPFS) (50% v 36% at 5 years; P =.041), and higher distant metastasis-free survival (DMFS) (86% v 57% at 5 years; P =.0013). However, there was no difference between the two treatment groups in the incidence of either acute or late high-grade RT-induced toxicity. Hematologic high-grade toxicity was more frequent in group II patients.
                As compared with Hfx RT alone, Hfx RT and concurrent low-dose daily CDDP offered a survival advantage, as well as improved LRPFS and DMFS. Failure to reach complete remission (CR) with chemotherapy in advanced stages of Hodgkin's disease is considered a poor prognostic factor for progression-free and overall survival. The role of radiotherapy after chemotherapy-induced remission is controversial.
                In 1989, the EORTC/GPMC started a randomized phase III trial on involved-field RT (IF-RT) after MOPP/ABV hybrid-induced remission in patients with stage III/IV Hodgkin's disease. In this ongoing trial, patients in CR after chemotherapy are randomized between IF-RT and no further treatment. Patients in partial remission (PR) all receive IF-RT. Patients, age 15-70 years, with previously untreated stage III/IV Hodgkin's disease are eligible. The randomized treatment arms are still blinded. The interim analysis of May 1996 focuses on the outcome of patients in chemotherapy-induced PR.
                A total of 405 of 493 registered patients were evaluable for response to chemotherapy. Fifty-nine percent of patients attained a CR, 37% a PR, and only 4% failed to respond. The IF-RT was actually given to 90% of the PR patients. After a median follow-up of 43 months, the five year progression-free and overall survival for patients in PR was 75% and 87%, respectively.
                IF-RT after MOPP/ABV-induced partial remission in stage III/IV Hodgkin's disease produces excellent failure-free and overall survival. Early intensification of treatment of this group of patients is not indicated. Despite their low risk for recurrence, many women with endometrial adenocarcinoma receive postoperative radiation therapy (RT). This study was developed to determine if adjunctive external beam irradiation lowers the risk of recurrence and death in women with endometrial cancer International Federation of Gynaecology and Obstetrics (FIGO) stages IB, IC, and II (occult disease).
                Four hundred forty-eight consenting patients with "intermediate risk" endometrial adenocarcinoma were randomized after surgery to either no additional therapy (NAT) or whole pelvic radiation therapy (RT). They were followed to determine toxicity, date and location of recurrence, and overall survival. A high intermediate risk (HIR) subgroup of patients was defined as those with (1) moderate to poorly differentiated tumor, presence of lymphovascular invasion, and outer third myometrial invasion; (2) age 50 or greater with any two risk factors listed above; or (3) age of at least 70 with any risk factor listed above. All other eligible participants were considered to be in a low intermediate risk (LIR) subgroup.
                Three hundred ninety-two women met all eligibility requirements (202 NAT, 190 RT). Median follow-up was 69 months. In the entire study population, there were 44 recurrences and 66 deaths (32 disease or treatment-related deaths), and the estimated 2-year cumulative incidence of recurrence (CIR) was 12% in the NAT arm and 3% in the RT arm (relative hazard (RH): 0.42; P=0.007). The treatment difference was particularly evident among the HIR subgroup (2-year CIR in NAT versus RT: 26% versus 6%; RH=0.42). Overall, radiation had a substantial impact on pelvic and vaginal recurrences (18 in NAT and 3 in RT). The estimated 4-year survival was 86% in the NAT arm and 92% for the RT arm, not significantly different (RH: 0.86; P=0.557).
                Adjunctive RT in early stage intermediate risk endometrial carcinoma decreases the risk of recurrence, but should be limited to patients whose risk factors fit a high intermediate risk definition. To report mature results of a randomized trial that compared extended-field radiotherapy (EFRT) versus pelvic radiotherapy with concomitant fluorouracil and cisplatin (CTRT) in women with locoregionally advanced carcinomas of the uterine cervix.
                Four hundred three women with cervical cancer were randomly assigned to receive either EFRT or CTRT. Patients were eligible if they had stage IIB to IVA disease, stage IB to IIA disease with a tumor diameter > or = 5 cm, or positive pelvic lymph nodes. Patients were stratified by stage and by method of lymph node evaluation.
                The median follow-up time for 228 surviving patients was 6.6 years. The overall survival rate for patients treated with CTRT was significantly greater than that for patients treated with EFRT (67% v 41% at 8 years; P <.0001). There was an overall reduction in the risk of disease recurrence of 51% (95% CI, 36% to 66%) for patients who received CTRT. Patients with stage IB to IIB disease who received CTRT had better overall and disease-free survival than those treated with EFRT (P <.0001); 116 patients with stage III to IVA disease had better disease-free survival (P =.05) and a trend toward better overall survival (P =.07) if they were randomly assigned to CTRT. The rate of serious late complications of treatment was similar for the two treatment arms.
                Mature analysis confirms that the addition of fluorouracil and cisplatin to radiotherapy significantly improved the survival rate of women with locally advanced cervical cancer without increasing the rate of late treatment-related side effects. We prospectively studied the efficacy of high dose therapy (HDT) versus an oral maintenance treatment (OMT) in patients with stage IV soft tissue sarcoma (STS).
                Both groups were pretreated with the CEVAIE combination consisting of carboplatin, etoposide, vincristine, actinomycin D, ifosfamide, and epirubicin. HDT consisted of a tandem cycle of thiotepa (600 mg/m(2)) plus cyclophosphamide (4,500 mg/m(2)) and melphalan (120 mg/m(2)) plus etoposide (1,800 mg/m(2)). This treatment was compared with OMT, consisting of four cycles trofosfamide (10 days 2 x 75 mg/m(2)/day) plus etoposide (10 days 2 x 25 mg/m(2)/day), and 4 cycles trofosfamide (10 days 2 x 75 mg/m(2)/day) plus idarubicin (10 days 4 x 5 mg/m(2)). Eligibility criteria were: diagnosis confirmed by reference pathology, primary stage IV, below 22 years of age, and having completed the study therapy.
                From 96 patients 45 were treated with HDT and 51 with OMT. The main risk parameters were equally distributed in both arms. After a median follow-up of 57.4 months, 11/45 (24.4%) patients in the HDT-arm and 26/51 (57.8%) patients in OMT-arm were alive. Kaplan-Meier analysis demonstrated an overall survival for the whole group of 0.27 (OMT group: 0.52, HDT group 0.27, log rank P = 0.03). The proportional hazard analysis for patients with rhabdomyosarcoma (RMS) or "RMS-like" tumors (77.1% of all patients) demonstrated an independent benefit of OMT on outcome.
                Oral maintenance therapy seems to be a promising option for patients with RMS-like stage IV tumors.
                (c) 2008 Wiley-Liss, Inc.
CRT seems to be optimal for most early stage (I-II) HD patients. For advanced stages (III to IV), CRT better prevents progression/relapse but CT alone seems to cause less SM.RT alone gives a higher overall SM risk than CRT due to increased need for salvage therapy. Reduced SM risk after IF-RT instead of EF-RT could not be demonstrated. Due to the large number of studies excluded because no IPD were received, to the inclusion of many outdated treatments and to the limited amount of long-term data, one must be cautious in applying these results to current therapies.