Update on the Role of Topotecan in the Treatment of Recurrent Ovarian Cancer

Abstract

Ovarian cancer is the fifth leading cause of cancer death in women. Most patients with ovarian cancer respond to first-line chemotherapy, but many relapse within 18 to 22 months. The development of efficacious salvage therapies that increase overall survival while maintaining quality of life is a great challenge in the treatment of this disease. Topotecan, a novel topoisomerase I inhibitor, is currently indicated for the treatment of recurrent metastatic carcinoma of the ovary. In patients with relapsed ovarian cancer, the overall response rates on treatment with topotecan range from 19%-33% in platinum-sensitive patients, 14%-18% in platinum-resistant patients, and 5%-11% in platinum-refractory patients. The proportion of patients achieving stable disease ranges between 17% in refractory and 48% in sensitive patients. In phase III studies, topotecan was shown to be equivalent in efficacy to both paclitaxel and liposomal doxorubicin as second-line therapy in patients with relapsed ovarian cancer. Further, non-cross-resistance between topotecan and paclitaxel was demonstrated in a third-line, phase III crossover study, suggesting that topotecan may be effective in the first-line setting with paclitaxel and/or platinum. Hematologic toxicities include neutropenia, thrombocytopenia, and anemia; however, these toxicities are usually short lived, noncumulative, and manageable with dose modifications, including low-dose topotecan regimens. Nonhematologic toxicities are usually mild to moderate in severity. These data support the use of topotecan for second-line therapy and suggest that topotecan may also be effective in first-line therapy. Further studies with topotecan alone and in combination with other agents are needed to fully characterize the role and sequencing of topotecan in the salvage and first-line settings. The Oncologist 2002;7(suppl 5):3-10

Topotecan in heavily pretreated patients with recurrent ovarian, peritoneal, and fallopian tube carcinoma

“…The finding that grade 3 and 4 neutropenia occurred in 69% of the patients corroborates other studies that demonstrated that myelosuppression, particularly neutropenia, is the dose‐limiting toxicity of topotecan (1,2,15,19,20) . We, however, could not find significant differences in toxicity in relation to the number of prior chemotherapy lines.…”

Topotecan in heavily pretreated patients with recurrent ovarian, peritoneal, and fallopian tube carcinoma

“…The finding that grade 3 and 4 neutropenia occurred in 69% of the patients corroborates other studies that demonstrated that myelosuppression, particularly neutropenia, is the dose-limiting toxicity of topotecan (1,2,15,19,20) . We, however, could not find significant differences in toxicity in relation to the number of prior chemotherapy lines.…”

Combined Directed Ortho Metalation/Cross-Coupling Strategies: Synthesis of the Tetracyclic A/B/C/D Ring Core of the Antitumor Agent Camptothecin

“…In the past 15 years, renewed synthetic interest in 1a and analogues 6 evolved due to findings that substituted derivatives of 1a such as 9-aminocamptothecin (1b), 7 9-((dimethylamino)methyl)-10-hydroxycamptothecin (Topotecan, 1c), 8 and Irinotecan (1d) 9 show low overall toxicity, higher solubility, and still impressive in vivo activity against certain solid tumors. In fact, Topotecan 1c and Irinotecan 1d were recently approved by the FDA for the treatment of ovarian cancer and small-cell lung cancer 10 and refractory colorectal cancer, respectively. 11 Alkaloids structurally related to camptothecin (1a) such as homocamptothecin (2), 12g,13 mappicine (3), 14,15 and mappicine ketone (4) 15 are also of clinical relevance.…”