Phase I trial of concomitant vinorelbine, cisplatin, and pelvic irradiation in cervical carcinoma and other advanced pelvic malignancies.
OBJECTIVE
To determine the maximum tolerated dose (MTD) of vinorelbine in combination with weekly cisplatin and pelvic radiation therapy (RT).


METHODS
Eligible patients included those with bulky or locally advanced cervical cancer. Women with other advanced gynecologic malignancies were also eligible. All patients received cisplatin 40 mg/m(-2)/week (maximum dose, 70 mg) during pelvic RT. Vinorelbine was administered on the same day as cisplatin at a starting dose of 10 mg/m(-2)/week and escalated in 5 mg/m(-2)/week increments. Dose-limiting toxicity (DLT) was defined as: grade 3-4 non-hematologic toxicity, grade 4 hematologic toxicity, or any toxicity which required > or =1 week delay in RT or an omission of >1 dose of chemotherapy.


RESULTS
Between April 2001 and September 2002, 12 women with pelvic malignancies (11 cervical, 1 recurrent ovarian) were enrolled. Cohorts of 3, 6, and 3 patients were treated at 10, 15, and 20 mg/m(-2)/week dose levels of vinorelbine. At the 20 mg/m2 level, DLT was observed. Two of three patients missed >1 cycle of chemotherapy secondary to predominantly hematologic toxicity. One patient at the 20 mg level developed a creatinine clearance <50 ml/min and missed 1 dose of cisplatin. Another developed transient grade 3 diarrhea. No grade 4 toxicities were observed.


CONCLUSIONS
The MTD of vinorelbine in combination with cisplatin and pelvic RT in patients with cervical cancer is 15 mg/m(-2)/week.
Mundt
Arno J
AJ
Department of Radiation and Cellular Oncology, University of Chicago Hospitals, Chicago, IL 60647, USA. mundt@rover.uchicago.edu
Rotmensch
Jacob
J
Waggoner
Steven E
SE
Yamada
S Diane
SD
Fleming
Gini F
GF
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001918:Brachytherapy / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010386:Pelvic Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077235:Vinorelbine
D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine