Maximum tolerated dose–Results of a phase I trial of paclitaxel and cisplatin with radiation therapy in carcinoma of the cervix

Abstract

13537 Background: Cisplatin based chemotherapy is the standard treatment for locally advanced carcinoma of the cervix. Recent studies have shown better response rates with treatment using newer combination chemotherapy regimens administered along with radiation therapy. The present study is a Phase I study, to establish the Maximal Tolerated Dose (MTD) of paclitaxel in combination with cisplatin as a radio sensitizer in the treatment of Carcinoma of the cervix and to analyze the toxicity profile of the combination regimen. Materials and Methods: 21 newly diagnosed patients with squamous cell carcinoma of the cervix stage (FIGO) I B to III B with good performance status (ECOG 0, 1) and with normal hepatic and renal parameters, were included in a Phase I trial to undergo concurrent chemoradiation with weekly paclitaxel and cisplatin. All eligible cohorts received external beam radiation therapy (50 Gy) given by conventional 4 field box technique. Concurrent chemotherapy was with weekly cisplatin (30 mg/m2) and an escalating dose level (according to the modified Fibonacci series) of weekly paclitaxel starting at 10 mg/m2 up to 50 mg/m2. This was followed by a single application of LDR brachytherapy. The maximum tolerated dose (MTD) of weekly paclitaxel was determined as 40 mg/m2. The dose limiting toxicity of this combination in our patients as occurred at a dose of 50 mg/m2 weekly paclitaxel, was grade 3 proctitis and vaginitis. Conclusion: In this Phase I trial of concurrent chemo radiation with weekly Paclitaxel at increasing doses and cisplatin (30 mg/m2) in patients with carcinoma of the cervix, the Maximum Tolerated Dose (MTD) was identified as paclitaxel (40 mg/m2). This combination was feasible, with an acceptable toxicity profile. This can be the recommended dose level in designing phase II studies. No significant financial relationships to disclose.