Phase I clinical trials in 85 patients with gynecologic cancer: the M. D. Anderson Cancer Center experience

Abstract

Objective: Disseminated gynecologic cancers are usually fatal due to chemoresistance. Recently, rationally developed, targeted agents are entering the early clinical trials setting. We assessed patients with metastatic gynecologic cancers in a dedicated phase I clinical trials clinic in order to determine their outcome.

Methods: We reviewed records for 89 consecutive patients with gynecologic cancers referred to the Phase I Clinical Trials Program, 85 (96%) of whom were treated on > or = 1 trial.

Results: Cancer diagnoses were ovarian (N=43), uterine (N=19), cervix (N=17), and other. Median age was 58 years; median number of prior cytotoxic regimens, five. Two patients (2.4%) achieved a CR; four (4.7%), a PR; and eight (9.4%), SD > or = 6 months (total CR/PR/SD > or = 6 months=16.5%) for the first phase I trial. Twenty-five patients enrolled on a second trial and three, on a third (N=113 trials total). Combining response data for all trials, of the 85 patients, two achieved CR (2.4%), nine achieved PR (10.6%), and 12 (14%) had SD for > or = 6 months. One-year survival was 30% (95% CI, 21% to 44%). There was no difference in time-to-treatment failure (TTF) on phase I versus the patient's last standard treatment.

Conclusion: Twenty-three of 85 patients (27%) with advanced, heavily pretreated, gynecologic cancers achieved CR/PR/SD > or = 6 months on a phase I trial, and overall TTF on phase I was comparable to that of last conventional therapy, suggesting that participation in a phase I trial is a reasonable option for these patients.

Figure 1

Panel A: 1^st phase I trial best RECIST response Waterfall plot of 85 patients showing best RECIST response to first phase I trial. Patients with progressive disease reflected by increase of at least 20 percent by RECIST, new lesions, or clinical progression are shown as an increase of 20%. Patients who were not evaluable were considered progressive and shown as an increase of 20%. Panel B: 2^nd phase I trial best RECIST response Waterfall plot of 25 patients showing best RECIST response to first phase I trial. Patients with progressive disease reflected by increase of at least 20 percent by RECIST, new lesions, or clinical progression are shown as an increase of 20%. Patients who were not evaluable were considered progressive and shown as an increase of 20%.

Figure 1

Panel A: 1^st phase I trial best RECIST response Waterfall plot of 85 patients showing best RECIST response to first phase I trial. Patients with progressive disease reflected by increase of at least 20 percent by RECIST, new lesions, or clinical progression are shown as an increase of 20%. Patients who were not evaluable were considered progressive and shown as an increase of 20%. Panel B: 2^nd phase I trial best RECIST response Waterfall plot of 25 patients showing best RECIST response to first phase I trial. Patients with progressive disease reflected by increase of at least 20 percent by RECIST, new lesions, or clinical progression are shown as an increase of 20%. Patients who were not evaluable were considered progressive and shown as an increase of 20%.

Figure 2. Paired time to treatment failure comparison (1^st phase I trial vs. last conventional treatment)

Paired time-to-treatment failure as plotted by Kaplan-Meier for first phase I therapy compared to the last conventional treatment before referral to the phase I clinic. Tic marks represent patients still on treatment and therefore censored at the time shown. Time-to-treatment failure was not significantly different between the first phase I treatment and the last conventional treatment.

Figure 3. Paired time to treatment failure comparison (2^nd phase I trial vs. last conventional treatment)

Paired time-to-treatment failure as plotted by Kaplan-Meier for second phase I therapy compared to the last conventional treatment before referral to the phase I clinic. Tic marks represent patients still on treatment and therefore censored at the time shown. There was a trend, albeit not statistically significant, towards a longer time-to-treatment failure for patients' second phase I trial as compared to their last conventional treatment.