Phase II study of sequential doublets: topotecan and carboplatin, followed by paclitaxel and carboplatin, in patients with newly diagnosed advanced ovarian cancer.
OBJECTIVE
Incorporating topotecan into standard platinum/taxane chemotherapy for advanced ovarian cancer has been complicated by myelosuppression. This study evaluated sequential doublets of topotecan and carboplatin, followed by paclitaxel and carboplatin, in newly diagnosed advanced ovarian cancer patients.


METHODS
Forty-five patients (median age, 56 years; range, 38-77 years) with stage III/IV disease and GOG performance status <2 were enrolled and received four cycles of topotecan (1.0 mg/m(2)/day on days 1 to 3) and carboplatin (AUC 4 on day 1), followed by four cycles of paclitaxel (175 mg/m(2) via 3-h IV infusion on day 1) and carboplatin (AUC 5 on day 1). All cycles were 21 days. Antitumor response was assessed after four and eight cycles; patients with clinical complete response (CR) underwent second-look laparotomy for determination of pathologic CR (PCR). Dose reductions were instituted for grade 4 neutropenia and thrombocytopenia, and for grade 3/4 nonhematologic toxicity.


RESULTS
Among 41 CA-125 evaluable patients, complete and partial responses were observed in 29 (70.7%) and 11 (26.8%) patients, respectively. Of the 12 clinical CRs (43%) in 28 evaluable patients, 10 patients underwent second-look laparotomy, with 3 PCRs (30%). Median time to progression was 14 months and actuarial survival was 23 months. Neutropenia was the primary toxicity and cause of dose adjustments and delays, including two deaths.


CONCLUSIONS
The antitumor activity observed is comparable with other series, although neutropenic complications were increased. Progression-free and actuarial survivals were slightly inferior. A Phase III trial (GOG 182) of sequential doublets in the reverse sequence is ongoing.
Texas Oncology, P.A., Charles A. Sammons Cancer Center, Dallas, TX 75246, USA. agordonmd@earthlink.net
Alan N
AN
Gordon
Lina
L
Asmar
Mark J
MJ
Messing
Daron G
DG
Street
Charles H
CH
Pippitt
Cheryl L
CL
Bailey
John
J
Savage
James A
JA
Young
D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D018394:CA-125 Antigen / Q000097:blood; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D018283:Cystadenocarcinoma, Papillary / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D018284:Cystadenocarcinoma, Serous / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D010534:Peritoneal Neoplasms / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects
D018394:CA-125 Antigen; D019772:Topotecan; D016190:Carboplatin; D017239:Paclitaxel