Studies of Chemotherapy in Cervical Cancer

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Abstract
SummaryA series of collaborative chemotherapy studies have been undertaken in Birmingham, UK, to identify single agent and combination chemotherapy regimens which may be of value in the palliation of advanced and recurrent cervical cancer and have potential for use as primary or adjuvant chemotherapy.Initially, 30 patients with symptomatic, recurrent cervical cancer were entered into a phase-II study of ifosfamide (5 g/m2 infused over 24 h every 21 days) with mesna. Ten of 30 patients showed objective response to treatment, and all of these reported subjective improvement of disease-related symptoms. Response rates in previously non-irradiated sites of disease (15 of 28) were significantly higher than for lesions arising in previously irradiated sites (4 of 22). Gastrointestinal, haematological, and urothelial toxicities were predictable and manageable, but an unpredictable severe central nervous system toxicity was observed in 3 patients.In view of the encouraging activity seen with IFO in this setting, further studies of IFO/mesna-associated CNS toxicity were performed. Using data from a study of 77 patients receiving IFO/mesna as treatment for a variety of advanced malignancies, a spectrum of EEG and clinical manifestations of IFO/mesna encephalopathy was defined and a grading system devised. Stepwise discriminant analysis of these data identified low pretreatment serum albumin concentration, high pretreatment serum creatinine concentration and the presence of disease below the level of the renal pedicles as variables associated with highest risk of developing severe CNS toxicity. A nomogram was devised which may be used to quantify the risk of an individual patient developing severe CNS toxicity with IFO/mesna treatment. Using the nomogram, patient selection may be rationalized and the few patients found to be at high risk of encephalopathy may be treated with alternative chemotherapy. IFO/mesna may be administered safely to the remaining majority of cases.Based upon these studies, a phase-II study of combination bleomycin (30 mg), ifosfamide (5 g/m2) and cis-platinum (50 mg/m2) (BIP), given every 28 days, has begun. Data from the first 19 évaluable patients include an overall response rate of 78% (2 complete and 13 partial responses). Toxicity was predictable and manageable. Further preliminary data from a pilot study indicate that the BIP regimen may be given safely and that effective cytoreduction may be achieved in around 80% of patients with locally advanced untreated cervical cancer prior to radical pelvic radiotherapy. A major collaborative trial is underway to determine whether this approach improves survival in patients with inoperable cervical cancer.

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