Neoadjuvant chemotherapy and radical surgery versus exclusive radiotherapy in locally advanced squamous cell cervical cancer: results from the Italian multicenter randomized study. Neoadjuvant versus adjuvant chemotherapy in premenopausal patients with tumours considered too large for breast conserving surgery: preliminary results of a randomised trial: S6. Randomized study of preoperative chemotherapy versus primary surgery for stage IB cervical cancer. The role of neoadjuvant intraarterial infusion chemotherapy with cisplatin and bleomycin for locally advanced cervical cancer. Randomized adjuvant trial of tamoxifen and goserelin versus cyclophosphamide, methotrexate, and fluorouracil: evidence for the superiority of treatment with endocrine blockade in premenopausal patients with hormone-responsive breast cancer--Austrian Breast and Colorectal Cancer Study Group Trial 5.
Neoadjuvant chemotherapy (NACT) and radical surgery (RS) have emerged as a possible alternative to conventional radiation therapy (RT) in locally advanced cervical carcinoma. In 1990, a phase III trial was undertaken to verify such a hypothesis in terms of survival and treatment-related morbidity.
                Patients with squamous cell, International Federation of Gynecology and Obstetrics stage IB2 to III cervical cancer were eligible for the study. They received cisplatin-based NACT followed by RS (type III to V radical hysterectomy plus systematic pelvic lymphadenectomy) (arm A) or external-beam RT (45 to 50 Gy) followed by brachyradiotherapy (20 to 30 Gy) (arm B).
                Of 441 patients randomly assigned to NACT+RS or RT, eligibility was confirmed in 210 and 199 patients, respectively. Treatment was administered according to protocol in 76% of arm A patients and 72% of arm B patients. Adjuvant treatment was delivered in 48 operated patients (29%). There was no evidence for any significant excess of severe morbidity in one of the two arms. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 58.9% and 55.4% for arm A and 44.5% and 41.3% for arm B (P =.007 and P =.02), respectively. Subgroup survival analysis shows OS and PFS rates of 64.7% and 59.7% (stage IB2-IIB, NACT+RS), 46.4% and 46.7% (stage IB2-IIB, RT) (P =.005 andP =.02), 41.6% and 41.9% (stage III, NCAT+RS), 36.7% and 36.4% (stage III, RT) (P =.36 and P =.29), respectively. Treatment had a significant impact on OS and PFS.
                Although significant only for the stage IB2 to IIB group, a survival benefit seems to be associated with the NACT+RS compared with conventional RT. The aim of this study was to assess a potential advantage in survival by neoadjuvant as compared to adjuvant chemotherapy. 414 premenopausal patients with T2-T3 N0-N1 M0 breast cancer were randomised to receive either four cycles of neoadjuvant chemotherapy (cyclophosphamide, doxorubicin, 5-fluorouracil), followed by local-regional treatment (group I) or four cycles of adjuvant chemotherapy after primary irradiation +/- surgery (group II). Surgery was limited to those patients with a persisting mass after irradiation, and aimed to be as conservative as possible. 390 patients were evaluable. With a median follow-up of 54 months, we observed a statistically significant difference (P = 0.039) in survival in favour of the neoadjuvant chemotherapy group. A similar trend was seen when the time to metastatic recurrence was evaluated (P = 0.09). At this stage, no difference in disease-free interval or local recurrence between these two groups could be observed. The mean total dose of chemotherapy administered was similar in both groups. On average, group I had more intensive chemotherapy regimes (doxorubicin P = 0.02) but fewer treatment courses (P = 0.008) as compared to the treated patients in group II. Haematological tolerance was reduced when chemotherapy succeeded to exclusive irradiation. Breast conservation was identical for both groups at the end of primary treatment (82 and 77% for groups I and II, respectively). Of the 191 evaluable patients in the neoadjuvant treatment arm, 65% had an objective response (> 50% regression) following four cycles of chemotherapy. The objective response rate to primary irradiation (55 Gy) was 85%. Improved survival figures in the neoadjuvant treatment arm could be the result of the early initiation of chemotherapy, but we cannot exclude that this difference might be attributable to a slightly more aggressive treatment. So far, the trend in favour of decreased metastases was not statistically significant. The local control appeared similar in both subgroups. To determine the most effective treatment and long-term outcome of patients with stage IB carcinoma of the cervix.
                From January 1999 to December 2001, 106 women with cervical cancer stage IB received neoadjuvant chemotherapy (n = 52) or primary surgery (n = 54). These were randomly assigned. Clinical effects and pathological changes were simultaneously recorded.
                The overall clinical response rate was 84.6% and included a complete response (CR) in four patients (7.7%), partial response (PR) in 40 patients (76.9%), and stable disease (SD) in the remaining eight patients (15.4%). Surgery revealed positive nodes in 9.6% neoadjuvant chemotherapy group patients and in 29.6% primary surgery group patients (P = 0.014). Similar results occurred with vascular space involvement: 27.8% in the primary surgery group compared to 9.6% in the neoadjuvant chemotherapy group (P = 0.024). However, parametrial infiltration was found in 7.4% of the patients in the primary surgery group, while only 3.8% showed it in the neoadjuvant chemotherapy group (P = 0.679). The overall 5-year survival rate was significantly higher for all patients who received neoadjuvant chemotherapy (84.6%) than for the control group (75.9%) (P = 0.0112). The median survival time in patients with complete response and partial response to chemotherapy (83.3 months) was significantly higher than that of patients with stable disease to chemotherapy (55.2 months) (P = 0.0049). 27.3% of patients developed recurrent disease within 5 years of the primary treatment. The women with recurrence included partial response in six patients (60.0%), and stable disease in four patients (40.0%). For the other patients there was partial response and complete response in 38 patients (90.5%), and stable disease in the remaining four patients (9.5%) (P = 0.035).
                Neoadjuvant chemotherapy can effectively eliminate the pathological risk factors and improve long-term survival in patients with locally advanced cervical cancer. To clarify the effect of neoadjuvant intraarterial infusion chemotherapy on the cure rate in advanced cervical cancer with bulky tumor, a total of 50 patients were examined prospectively. The clinical stage according to the International Federation of Gynecology and Obstetrics (FIGO) classification included 23 IIb, 6 IIIa, and 21 IIIb. These patients were randomly divided into the neoadjuvant intraarterial infusion chemotherapy group and the control group. There were no significant differences in mean age, FIGO clinical stage, and tumor histology between groups. Twenty-five patients in the former group were given 25 mg/m2 of cisplatin and 15 mg/m2 of bleomycin via each internal iliac artery. If the results of the evaluation indicated that surgery was feasible, radical surgery was performed. The patients whose tumors were inoperable received radiation therapy consisting of external irradiation and intracavitary irradiation. Twenty-five patients in the control group also underwent the same radiation therapy. The overall response rate was 80.0%. Eighteen of 20 responders underwent surgery. The 3-year survival rate was 85.7% for operated patients, 42.9% for patients receiving neoadjuvant intraarterial infusion chemotherapy followed by irradiation, and 49.5% for the control group. In the present study, neoadjuvant intraarterial infusion chemotherapy did not improve the prognosis of patients with advanced cervical cancer compared to radiation therapy alone, and only responders who underwent surgery obtained an advantage in survival. Effective adjuvant treatment modalities in premenopausal breast cancer patients today include chemotherapy, ovariectomy, and tamoxifen administration. The purpose of Austrian Breast and Colorectal Cancer Study Group Trial 5 was to compare the efficacy of a combination endocrine treatment with standard chemotherapy.
                Assessable trial subjects (N = 1,034) presenting with hormone-responsive disease were randomized to receive either 3 years of goserelin plus 5 years of tamoxifen or six cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF). Stratification criteria included tumor stage and grade, number of involved nodes, type of surgery, and steroid hormone receptor content. Relapse-free survival (RFS) was defined as time from randomization to first relapse, local recurrence, or contralateral incidence, and overall survival (OS) as time to date of death.
                With a 60-month median follow-up, 17.2% of patients in the endocrine group and 20.8% undergoing chemotherapy developed relapses. Local recurrences emerged in 4.7% and 8.0%, respectively. RFS and local recurrence-free survival differed significantly in favor of endocrine therapy (P =.037 and P =.015), with a similar trend observed in OS (P =.195).
                Overall, our data suggest that the goserelin-tamoxifen combination is significantly more effective than CMF in the adjuvant treatment of premenopausal patients with stage I and II breast cancer.
Both OS and PFS were improved with neoadjuvant chemotherapy. Although the effects were less clear on all other pre-specified outcomes, they all tended to be in favour of neoadjuvant chemotherapy. Whilst these results appear to indicate that neoadjuvant chemotherapy may offer a benefit over surgery alone for women with early-stage or locally-advanced cervical cancer, the evidence is based on only a small number of trials, and further research may be warranted.