Maximum tolerated dose and early response - results of a phase I trial of paclitaxel and cisplatin with radiation therapy in carcinoma of the cervix.

AIMS

Cisplatin-based chemotherapy with radiotherapy is currently the standard treatment for locally advanced carcinoma of the cervix. Recent studies have shown a better response with the addition of newer chemotherapeutic agents. The aim of this phase I study was to establish the maximum tolerated dose (MTD) of paclitaxel in combination with cisplatin as a radiosensitiser along with radiation therapy in the treatment of carcinoma of the cervix and to analyse the toxicity profile of the combination regimen.

MATERIALS AND METHODS

In total, 21 newly diagnosed patients with squamous cell carcinoma of the cervix, International Federation of Gynecology and Obstetrics stage IB to IIIB were included in this trial. All patients received external beam radiation therapy to the pelvis (50 Gy in 25 fractions) delivered by conventional four-field box technique followed by low dose rate brachytherapy. Concurrent chemotherapy was administered with weekly cisplatin (30 mg/m(2)) and an escalating dose of weekly paclitaxel starting at 10 mg/m(2) up to 50 mg/m(2) (according to the modified Fibonacci series).

RESULTS

The MTD of weekly paclitaxel was found to be 40 mg/m(2). The dose-limiting toxicity that occurred in our patients at a dose of 50 mg/m(2) weekly paclitaxel was grade 3 proctitis and vaginitis.

CONCLUSION

In this phase I trial of concurrent radiation and combination chemotherapy with weekly paclitaxel and cisplatin (30 mg/m(2)/week), the MTD of paclitaxel was found to be 40 mg/m(2). This combination was feasible, with an acceptable toxicity profile.