N-Methylformamide in advanced squamous cancer of the uterine cervix: An Eastern Cooperative Oncology Group phase II trial

Purpose: Preclinical and clinical data support the study of polar-planar compounds such as N-Methylformamide (NMF) in advanced squamous cell carcinoma of the uterine cervix (SCC). This phase II trial sought to determine the efficacy and toxicities of NMF in patients with advanced SCC. Patients and methods: Eligibility for this trial required bidimensionally measurable squamous or adenosquamous cell cancer of the uterine cervix incurable by surgery or radiation therapy, ECOG performance status of ≤2, no prior NMF and no more than one prior chemotherapy regimen. Patients received NMF at 2000 mg/m ² intravenously over 15-30 minutes days 1, 8 and 15. The cycle was repeated every 42 days. A single dose escalation of 25%, 500 mg/m ² was made after the first cycle if the toxicities did not exceed grade I for hepatic toxicity and grade II for nausea and vomiting. Results: From July 1987 through September 1998, 21 patients with advanced squamous cell carcinoma of the uterine cervix were entered on study. Two patients were ineligible because there was no pretreatment SGOT on one and the other deteriorated prior to drug approval. Therefore, 19 patients were include in the analysis of response and survival. Four were inevaluable, three due to inappropriate tumor evaluation and one secondary to grade III vomiting, who went off study. These patients were included in the denominator while computing the results. There were 2 deaths, one due to pulmonary hemorrhage from perforation during central venous insertion and one due to disease. 30% (6/19) patients had toxicities, Eastern Cooperative Oncology Group (ECOG) grade III or higher and 2 of these patients suffered multiple grade III toxicities. There were no complete or partial responses. Conclusion: In this population, NMF in the dose and schedule employed exhibited no clinical activity.