Radiation therapy with concomitant paclitaxel and cisplatin chemotherapy in cervical carcinoma limited to the pelvis: a phase I/II study of the Gynecologic Oncology Group.
OBJECTIVE
To determine the maximum tolerated dose (MTD) of weekly paclitaxel and cisplatin chemotherapy concurrent with whole pelvic irradiation in women with locally advanced cervical cancer.


METHODS
Consenting patients with stage IB2, IIA, IIB, IIIB and IVA carcinoma of the cervix (all cell types) were eligible for this phase I/II trial. Chemotherapy agents were administered in escalating doses to cohorts of three patients at each dose level, pending evaluation of toxicities from the previous dose level.


RESULTS
Thirty-five eligible women were enrolled on this study, of whom 13 comprised the phase I component. The MTD was determined to be cisplatin 40 mg/m2 and paclitaxel 40 mg/m2 administered weekly for six cycles with external beam radiation therapy. An additional 21 patients were enrolled in the phase II component at the previously determined MTD, yielding a total of 22 patients at the MTD, of whom 19 were evaluable. Among the evaluable patients treated at the MTD, two had grade 3 or 4 gastrointestinal (GI) toxicities (representing 5 of 113 cycles administered to this cohort) and seven experienced grade 3 or 4 neutrophil toxicity, none occurring prior to the fourth cycle. Thrombocytopenia was rare. Radiation therapy was successfully completed in 52% of patients at 8 weeks and in 79% of patients at 9 weeks, with a median of 59 days.


CONCLUSIONS
Paclitaxel and cisplatin combination chemotherapy concurrent with whole pelvic irradiation can be safely administered at the described MTD.
DiSilvestro
Paul A
PA
Program in Womens Oncology, Women and Infants Hospital, 101 Dudley Street, Providence, RI 02905, and Division of Gynecologic Oncology, University of Oklahoma, Oklahoma City 73190, USA. pdisilvestro@wihri.org
Walker
Joan L
JL
Morrison
Astrid
A
Rose
Peter G
PG
Homesley
Howard
H
Warshal
David
D
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D011829:Radiation Dosage; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*
D017239:Paclitaxel; D002945:Cisplatin