Gemcitabine and oxaliplatin followed by paclitaxel and carboplatin as first line therapy for patients with suboptimally debulked, advanced epithelial ovarian cancer. A phase II trial of sequential doublets. The GO-First Study.
OBJECTIVE
Gemcitabine and oxaliplatin are active in epithelial ovarian cancer with minimal overlapping toxicity. We studied the efficacy and toxicity of this combination in patients with advanced ovarian cancer when given prior to carboplatin and paclitaxel.


METHODS
Chemonaive patients with epithelial ovarian cancer and measurable disease were eligible for the study. Treatment consisted of gemcitabine 1250 mg/m2 on days 1 and 8 and oxaliplatin 130 mg/m2 on day 8 every 21 days (GO) for 4 cycles. This was followed by carboplatin AUC = 6 and paclitaxel 175 mg/m2 on day 1 every 21 days (CP) for 4 cycles.


RESULTS
Twenty patients, median age 62 years (range 39-78), FIGO stages III (16) and IV (4) received treatment. The response rate (RR) after 4 cycles of GO was 80% (95%CI 61-99%) (4 complete responses (CR), 12 partial responses (PR)). Interval debulking surgery was performed in 7 patients (35%). After CP chemotherapy, RR increased to 85% (95%CI 68-100%) (CR = 13, PR = 4). Median time to progression was 14.5 months. Estimated median overall survival was 31.5 months. Toxicities of GO were mild; grade 3/4 nausea in 3 patients (15%) and vomiting in 2 patients (10%), grade 3/4 neutropenia in 5 patients (25%). Grade 2/3 peripheral neuropathy occurred in 5 patients (25%). After sequential administration of CP, grade 2/3 neuropathy occurred in 13 patients (72%).


CONCLUSIONS
The sequential doublet regimen of GO followed by CP resulted in unacceptable neurotoxicity and is not recommended for further study; however, the doublet gemcitabine and oxaliplatin has significant activity in the first line treatment of patients with ovarian cancer.
Steer
C B
CB
Department Medical Oncology, Guys and St Thomas's NHS Trust, London, UK. christopher.steer@bordermedonc.com.au
Chrystal
K
K
Cheong
K A
KA
Galani
E
E
Marx
G M
GM
Strickland
A H
AH
Yip
D
D
Lofts
F
F
Gallagher
C
C
Thomas
H
H
Harper
P G
PG
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000601:surgery; D000077150:Oxaliplatin; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D015996:Survival Rate; D000093542:Gemcitabine
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D016190:Carboplatin; D017239:Paclitaxel; D000093542:Gemcitabine