A phase I study of docetaxel as a radio-sensitizer for locally advanced squamous cell cervical cancer.
OBJECTIVE
This study was designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of weekly docetaxel with concurrent radiotherapy (RT) for the primary treatment of locally advanced squamous cell carcinoma of the cervix.


METHODS
Eligible patients included those with locally advanced squamous cell cervical cancer without para-aortic lymph node involvement. Docetaxel dose levels were 20 mg/m(2), 30 mg/m(2) and 40 mg/m(2) given intravenously weekly for 6 cycles. Three patients were to be treated at each dose level and 6 to receive the MTD.


RESULTS
Fifteen patients completed 4-6 cycles of chemotherapy. One of three patients experienced 2 delayed grade 3 severe adverse events (SAE) at the 20 mg/m(2) dose level consisting of colonic and ureteral obstruction. At the 30 mg/m(2) dose level, 1/4 patients had a probable treatment-related celiotomy due to obstipation and a necrotic tumor. Of the 8 patients treated at the 40 mg/m(2) dose level, 1 experienced grade 3 pneumonitis, likely treatment related. Overall, 10/15 (67%) experienced grade 1 or 2 diarrhea, 6 had grade 2 hematologic toxicity, and 2 had grade 2 hypersensitivity. 10 of 16 patients (67%) had no evidence of disease with follow-up ranging from 10-33 months (average 23 months).


CONCLUSIONS
The recommended phase II dose of docetaxel administered weekly with concurrent radiotherapy for locally advanced squamous cell carcinoma of the cervix is 40 mg/m(2).
Alvarez
Edwin A
EA
Department of Reproductive Medicine, Division of Gynecologic Oncology, Moores UCSD Cancer Center, La Jolla, CA 92093-0987, USA. E1alvarez@ucsd.edu
Wolfson
Aaron H
AH
Pearson
J Matt
JM
Crisp
Meredith P
MP
Mendez
Luis E
LE
Lambrou
Nicholas C
NC
Lucci
Joseph A
JA
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D011838:Radiation-Sensitizing Agents / Q000009:adverse effects* / Q000627:therapeutic use; D043823:Taxoids / Q000009:adverse effects* / Q000627:therapeutic use; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*
D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D043823:Taxoids; D000077143:Docetaxel