A phase I/II study of extended field radiation therapy with concomitant paclitaxel and cisplatin chemotherapy in patients with cervical carcinoma metastatic to the para-aortic lymph nodes: a Gynecologic Oncology Group study.
OBJECTIVE
To determine the maximum tolerated dose (MTD) of weekly paclitaxel and cisplatin chemotherapy concurrent with extended field irradiation in women with cervical cancer metastatic to the para-aortic nodes.


METHODS
Patients with carcinoma of the cervix and histologically documented para-aortic node metastases were eligible for this phase I/II trial. Chemotherapy agents were administered weekly concurrent with extended field radiation with escalating doses of paclitaxel from 30-50 mg/m(2) in each of three cohorts of three patients each. A phase II cohort was then evaluated at the selected maximum tolerated dose (MTD).


RESULTS
The MTD was determined to be cisplatin 40 mg/m(2) (maximum dose of 70 mg) and paclitaxel 40 mg/m(2) administered weekly for six cycles concurrent with extended field radiation therapy. There were 19 evaluable patients for the phase II analysis of toxicity and efficacy. Grade three and four gastrointestinal toxicity was seen in 6 and neutropenia in 7. Radiation therapy was successfully completed in 36.8% of patients at eight weeks and in 68.4% of patients at nine weeks, with a median time to completion was 56 days. A total of 27 evaluable patients were enrolled, twelve are dead (mean survival of those deceased is 25 months), and 15 (56%) are alive, and have been followed for a mean of 48 months (range 25-68; median of 46 months).


CONCLUSIONS
Paclitaxel and cisplatin combination chemotherapy concurrent with extended field pelvic para-aortic irradiation can be administered at the described MTD and shows a higher than previously reported disease-free survival in relation to historical data. The 56% survival to date, and 50% estimated 48 month survival, warrants validation in a larger prospective cohort. Central radiation dose reduction is being considered in the next trial to decrease late toxicity of regimen.
Walker
Joan L
JL
Division of Gynecologic Oncology, University of Oklahoma, Oklahoma City, OK 73190, USA. joan-walker@ouhsc.edu
Morrison
Astrid
A
DiSilvestro
Paul
P
von Gruenigen
Vivian E
VE
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D001918:Brachytherapy; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D015331:Cohort Studies; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*
D017239:Paclitaxel; D002945:Cisplatin