Phase I-II study of irinotecan (CPT-11) plus nedaplatin (254-S) with recombinant human granulocyte colony-stimulating factor support in patients with advanced or recurrent cervical cancer.
Combination chemotherapy with irinotecan (CPT-11) and platinum compounds is effective for treating cervical cancer. Nedaplatin (254-S) is a new cisplatin analogue that achieves a high response rate (53%) in patients with primary cervical cancer. We performed a phase I-II study of combination chemotherapy with CPT-11 plus 254-S for advanced or recurrent cervical cancer. The inclusion criteria were stage IV disease or recurrence. CPT-11 and 254-S were administered intravenously on day 1, while rhG-CSF (50 microg) was given on days 3-12. This regimen was repeated after 4 weeks. Dose escalation was carried out in tandem (CPT-11/254-S: 50/70, 50/80, and 60/80 mg m(-2)). A total of 27 patients (stage IV=seven, recurrence=20) were enrolled. The phase I study enrolled eight patients. At dose levels 1 and 2, no dose-limiting toxicities were observed. At dose level 3, the first two patients developed DLTs. The maximum tolerated dose of CPT-11 and 254-S was 60 and 80 mg m(-2), respectively, and the recommended doses were 50 and 80 mg m(-2). Grade 3/4 haematologic toxicity occurred in 67% in phase II study, but there were no grade 3 non-haematologic toxicities except for nausea or lethargy. In all 27 patients, there were two complete responses (7%) and 14 Partial responses (52%), for an overall response rate of 59% (95% confidence interval: 39-78%). Among the 12 responders with recurrent disease, the median time to progression and median survival were 161 days (range: 61-711 days) and 415 days (range: 74-801 days). This new regimen is promising for cervical cancer.
Tsuda
H
H
Department of Obstetrics and Gynecology, 2-13-22, Miyakojimahondori Miyakojima, Osaka 534-0021, Japan. tsud777@ocgh.hospital.city.osaka.jp
Hashiguchi
Y
Y
Nishimura
S
S
Miyama
M
M
Nakata
S
S
Kawamura
N
N
Negoro
S
S
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use / Q000633:toxicity*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D000077146:Irinotecan; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D011994:Recombinant Proteins; D012008:Recurrence; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D009944:Organoplatinum Compounds; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000077146:Irinotecan; C053989:nedaplatin; D002166:Camptothecin