An open-label, single-arm Phase II study of intravenous weekly (Days 1 and 8) topotecan in combination with carboplatin (Day 1) every 21 days as second-line therapy in patients with platinum-sensitive relapsed ovarian cancer.
OBJECTIVE
To evaluate clinical activity of weekly topotecan plus carboplatin in patients with platinum-sensitive recurrent ovarian, fallopian tube, or peritoneal carcinoma.


METHODS
An open-label, single-arm, multicenter Phase I/II study. Phase II was the activity assessment phase, with overall response rate (ORR) as the primary endpoint. Eligible patients (females aged ≥18 years) received study treatment at the maximum-tolerated dose (MTD) identified in Phase I: intravenous topotecan 2.5mg/m(2) (Days 1 and 8), followed by carboplatin AUC 5 (Day 1), every 21 days. A two-stage Green-Dahlberg design was used to assess efficacy of treatment. An ORR of ≤30% was required to conclude that treatment was ineffective.


RESULTS
Twenty-two patients in Phase I permitted identification of the MTD. In Phase II, 55 patients (median age 64.0 years) were enrolled and included in the intent-to-treat population. There were six complete responses (10.9%) and 11 partial responses (20.0%), giving an ORR of 30.9% (17 patients; 95% CI: 18.7%, 43.1%). Median time to response and progression-free survival were 6.57 weeks (95% CI: 5.86, 12.57) and 44.29 weeks (95% CI: 36.14, 52.14), respectively. Grade 3/4 hematological toxicity caused dose reductions, treatment delays and study discontinuation. Neutropenia (Grade 3: 29%; Grade 4: 11%) was the most common hematological adverse event (AE). Fatigue (71%) and nausea (71%) were the most common drug-related non-hematologic AEs.


CONCLUSIONS
This study showed an acceptable benefit-risk profile for topotecan plus carboplatin. Further studies using alternative dose levels could help define an optimal dosing schedule for this treatment combination in patients with platinum-sensitive recurrent disease.
Division of Gynecologic Oncology, Cleveland Clinic and MetroHealth Medical Center, 9500 Euclid Avenue, Cleveland, OH 44195, USA. rosep@ccf.org
Peter G
PG
Rose
Bradley J
BJ
Monk
Diane
D
Provencher
Jean
J
Hartney
Philippe
P
Legenne
Stephen
S
Lane
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects
D019772:Topotecan; D016190:Carboplatin