Weekly gemcitabine and cisplatin in combination with pelvic radiation in the primary therapy of cervical cancer: a phase I trial of the Puget Sound Oncology Consortium.
OBJECTIVE
Define the maximum tolerated dose of weekly gemcitabine given concomitantly with standard weekly cisplatin and pelvic radiotherapy for primary treatment of cervical cancer.


METHODS
Gemcitabine at specified dose levels was given concomitantly with weekly cisplatin at 40 mg/m2 for six cycles with concurrent radiotherapy in primary therapy of stage IB-IVA cervix cancer. Radiation consisted of 4500-5000 cGy in 25 daily fractions combined with brachytherapy to take point A to > or = 8500 cGy.


RESULTS
At gemcitabine 100 mg/m2, three of six patients demonstrated a dose limiting toxicity (DLT). At gemcitabine 50 mg/m2, two of two had DLTs. DLTs consisted of severe fatigue, lymphopenia, diarrhea, and tinnitus. All patients had a clinical complete response; four pathologically confirmed. Two patients recurred outside the radiated field and seven are disease-free (median follow-up 30 months). Following the second DLT at gemcitabine 50 mg/m2, the trial was stopped according to predetermined criteria.


CONCLUSIONS
Adding low dose weekly gemcitabine to cisplatin and pelvic radiotherapy resulted in an excellent response but unacceptable toxicities. Addition of gemcitabine prior to weekly cisplatin with radiation for cervical cancer will likely require reduction of cisplatin doses.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington, 1959 N.E. Pacific St., Box 356460, Seattle, WA 98195-6460, USA. swishere@u.washington.edu
Swisher
Elizabeth M
EM
Swensen
Ron E
RE
Greer
Benjamin
B
Tamimi
Hisham
H
Goff
Barbara A
BA
Garcia
Rochelle
R
Koh
Wui-Jin
WJ
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001918:Brachytherapy; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D000093542:Gemcitabine
D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine