Neoadjuvant chemotherapy in locally advanced cervical cancer: two randomised studies.

Between August 1990 and January 1992, 184 patients with squamous cell carcinoma of the cervix, FIGO stage II B IV A were randomised (study 1) to receive either two cycles of bleomycin, ifosfamide-mesna and cisplatin (BIP) chemotherapy (CT) followed by radiotherapy (RT) 'CT-RT Group' n = 94 or RT alone, RT Group n = 90. In the 'CT-RT Group', of evaluable 89 patients, 64 responded: complete response (CR) four (4.5%) and partial response (PR) 60 (67.5%). Of the remaining 25 patients 23 had stable disease and two progressed. Eighty of 89 patients completed RT as planned. Following RT 56 (70%) achieved CR, 19 (23.7%) had residual disease and five (6.3%) had progressed. Patients aged > 45 and those with Hb > 10 gm/dL had significantly better response to CT. Further, CT responders had a better response to RT; 83% (49/59) vs 33.3% (seven/21), p < 0.01. In the 'RT Group' 88 patients were evaluable; 61 (69.3%) patients achieved CR, 25 had residual disease and two progressed. The estimated overall survival at 48 months in the 'CT-RT Group' and the 'RT Group' is 38% +2.01 (SE) and 36% +1.85 (SE), p = 0.59 respectively. In a subsequent randomised study (study 2) 36 patients with stage III B cervical cancer received three cycles of BIP (as above) followed by RT vs 36 patients who received RT alone. In the 'CT-RT Group' 29 patients responded; CR-8 (22.2%), PR-21 (58.3%). Six patients had no response to CT and one patient died of CT toxicity. Following RT-24 of 35 (68-6%) patients achieved CR, eight had residual disease and three patients progressed while on RT. In the 'RT Group'-21 of 36 (58.4%) achieved CR, 12 had residual disease and three progressed. Estimated survival was 71% in the 'CT-RT Group' and 69% in the 'RT Group', p = ns. Nausea/vomiting, alopecia, grade I-II myelosuppression, diarrhoea and mucositis were the major side effects of CT. Three patients died of CT toxicity-two in study 1 and one in study 2. Cystitis, proctitis and local skin reaction after RT occurred equally in the two groups in both the studies. BIP CT prior to RT in patients with locally advanced cervical cancer results in a high response rate. Response to CT predicts response to RT. There is no increase in the toxicity to subsequent RT. Our studies have failed to demonstrate any significant difference in overall and disease-free survival when neoadjuvant CT is added prior to the standard RT regimen.

RCT Entities:   Population Interventions Outcomes