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

A comparison of patients with relapsed and chemo-refractory gestational trophoblastic neoplasia

“…These findings are consistent with data from other tumour types such as ovary and testis, which demonstrate a difference in outcome regarding patients with refractory and relapsed disease (Thigpen et al, 1993;McCaffrey et al, 1997;Herzog, 2002).…”

Management of Treatment-Related Toxicity in Advanced Ovarian Cancer

“…In agreement with the findings of Goldwasser et al, fewer patients required blood cell transfusions or growth factor support to manage the hematologic toxicity of topotecan during later courses of therapy. Although no absolute remission data could be generated from that study, all of the patients achieved a complete or partial remission or stable disease during the course of topotecan treatment [64]. That study supports the safe and long-term use of topotecan as palliative therapy for the advanced ovarian cancer patient.…”

Emerging Role of Topotecan in Front-Line Treatment of Carcinoma of the Ovary

“…An ORR (both cohorts) of 12% was observed, including partial responses (PRs) in 2 of 22 patients initially progressing on topotecan and 3 of 35 patients initially progressing on paclitaxel when they received their third-line therapy [27]. The results of these studies suggest that prior treatment with topotecan or paclitaxel may not adversely affect future responses to the crossover treatment [12]. Additionally, albeit limited by patient numbers, these findings suggest that patients could benefit from receiving topotecan in a front-line strategy because topotecan had activity against tumors that were resistant to both platinum and paclitaxel.…”

“…The U.S. Food and Drug Administration approved the agent in 1996 for the treatment of metastatic carcinoma of the ovary after failure of first-or second-line chemotherapy. Several studies have demonstrated the efficacy of topotecan as a second-line therapy, with tumor response rates ranging from 13%-33% [6][7][8][9][10][11], (review by Herzog pp 3-10 [12]). The maximum tolerated dose (MTD) of topotecan was 1.5 mg/m 2 /day using a 5-day regimen every 21 days.…”