Randomized comparison of weekly cisplatin or protracted venous infusion of fluorouracil in combination with pelvic radiation in advanced cervix cancer: a gynecologic oncology group study.
OBJECTIVE
Concurrent chemoradiotherapy is the standard of care for locally advanced cervix cancer; the optimal chemotherapy regimen is not yet defined. This trial was designed to compare the outcome of protracted venous infusion (PVI) fluorouracil (FU) with standard weekly cisplatin and concurrent radiation therapy (RT).


METHODS
Patients with stage IIB, IIIB, and IVA cervical cancer with clinically negative aortic nodes were eligible. Pelvic RT dose was 45 Gy with a parametrial boost to involved sides of 5.4 to 9 Gy, and high- or low-dose rate intracavitary brachytherapy. Standard therapy was weekly cisplatin 40 mg/m2, and experimental therapy was PVI FU 225 mg/m2/d for 5 d/wk for six cycles during RT.


RESULTS
The study was closed prematurely when a planned interim futility analysis indicated that PVI FU/RT had a higher treatment failure rate (35% higher) and would, most likely, not result in an improvement in progression-free survival compared with weekly cisplatin/RT. The PVI FU/RT arm continues to show a higher risk of treatment failure (relative risk [RR] unadjusted, 1.29) and a higher mortality rate (RR unadjusted, 1.37). There was no difference in pelvic treatment failure between regimens, but there was an increase in the failure rate at distant sites in the PVI FU arm.


CONCLUSIONS
In this study, PVI FU does not show improved outcome over weekly cisplatin. Future research should explore combinations of FU with cisplatin, new radiosensitizers, and active drugs combined with RT to reduce the high rate of pelvic and distant treatment failure still seen in advanced cervix cancer.
Lanciano
Rachelle
R
Department of Radiation Oncology, Delaware County Memorial Hospital, Drexel Hill, PA 19026, USA. rlancmd@aol.com
Calkins
Alison
A
Bundy
Brian N
BN
Parham
Groesbeck
G
Lucci
Joseph A
JA
Moore
David H
DH
Monk
Bradley J
BJ
O'Connor
Dennis M
DM
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D016019:Survival Analysis; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*
D002945:Cisplatin; D005472:Fluorouracil