Weekly gemcitabine and cisplatin in combination with pelvic radiation in the primary therapy of cervical cancer: a phase I trial of the Puget Sound Oncology Consortium.

OBJECTIVE: Define the maximum tolerated dose of weekly gemcitabine given concomitantly with standard weekly cisplatin and pelvic radiotherapy for primary treatment of cervical cancer.
METHODS: Gemcitabine at specified dose levels was given concomitantly with weekly cisplatin at 40 mg/m2 for six cycles with concurrent radiotherapy in primary therapy of stage IB-IVA cervix cancer. Radiation consisted of 4500-5000 cGy in 25 daily fractions combined with brachytherapy to take point A to > or = 8500 cGy.
RESULTS: At gemcitabine 100 mg/m2, three of six patients demonstrated a dose limiting toxicity (DLT). At gemcitabine 50 mg/m2, two of two had DLTs. DLTs consisted of severe fatigue, lymphopenia, diarrhea, and tinnitus. All patients had a clinical complete response; four pathologically confirmed. Two patients recurred outside the radiated field and seven are disease-free (median follow-up 30 months). Following the second DLT at gemcitabine 50 mg/m2, the trial was stopped according to predetermined criteria.
CONCLUSIONS: Adding low dose weekly gemcitabine to cisplatin and pelvic radiotherapy resulted in an excellent response but unacceptable toxicities. Addition of gemcitabine prior to weekly cisplatin with radiation for cervical cancer will likely require reduction of cisplatin doses.