Alternate Dosing Schedules for Topotecan in the Treatment of Recurrent Ovarian Cancer

Morris, R.

doi:10.1634/theoncologist.7-2004-29

Cited by 10 publications

(12 citation statements)

References 11 publications

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“…or bolus infusion. A summary of the tolerability and antitumor activity of weekly topotecan clinical trials in ovarian cancer patients is presented in Table 5 [19,24,29,57]. Two clinical trials of continuous i.v.…”

Section: Weekly Topotecan Therapymentioning

confidence: 99%

Topotecan Dosing Guidelines in Ovarian Cancer: Reduction and Management of Hematologic Toxicity

Armstrong

2004

The Oncologist

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Topotecan dosing considerations and alternative dosing schedules to reduce and manage myelosuppression during the treatment of relapsed ovarian cancer were reviewed. The myelosuppression patterns from phase I, II, and III clinical trials were analyzed to evaluate the degree of hematologic toxicity and to determine risk factors predictive of myelosuppression. Additionally, recent publications of alternative topotecan doses and schedules were examined. Extent of prior therapy, prior platinum therapy (particularly carboplatin), advanced age, impaired renal function, and prior radiation therapy were identified as potential risk factors for greater hematologic toxicity after topotecan therapy. Reducing the starting topotecan dose to 1.0 or 1.25 mg/m 2 /day is recommended to reduce the incidence of severe myelosuppression in high-risk individuals receiving topotecan for 5 consecutive days. Hematopoietic growth factors, transfusion therapy, and schedule adjustments may also help manage myelosuppression. Alternative schedules of 3-day or weekly dosing appear to have less myelotoxicity and are currently under evaluation. The clinical aspects of topotecan-related myelosuppression and results from clinical trials indicate that the dose, and possibly the dosing schedule, of topotecan can be modified to reduce hematologic toxicity and improve tolerance without compromising efficacy. Prospective individualization of topotecan dosing may prevent or minimize dose-limiting myelosuppression and allow patients to achieve the maximum topotecan benefit by improving their ability to complete therapy with fewer treatment delays. Ongoing clinical trials evaluating alternative dosing schedules with superior hematologic tolerability may facilitate the inclusion of topotecan in combination regimens for patients with ovarian cancer. Proposed topotecan dosing guidelines to reduce and manage myelosuppression are outlined.

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Section: Weekly Topotecan Therapymentioning

confidence: 99%

Topotecan Dosing Guidelines in Ovarian Cancer: Reduction and Management of Hematologic Toxicity

Armstrong

2004

The Oncologist

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“…To optimize efficacy and patient convenience while striving to decrease toxicity, alternative dosing strategies are being examined, including 21-day continuous infusion, daily × 3, and weekly schedules ( [26] and see Morris review pp 29-35 [27]). These alternate dosing regimens may allow for better toxicity profiles, sparing hematopoietic and mucosal progenitor cells while maintaining the therapeutic efficacy of topotecan treatment [28].…”

Section: Alternative Dosing Strategiesmentioning

confidence: 99%

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

Herzog

2002

The Oncologist

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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

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“…However, the tolerability of this regimen may be lower in patients with poor performance status, advanced age, or comorbidities. Alternative dosing regimens and pathways of administration that have better tolerability while maintaining prolonged exposure have been investigated (7,8,26,37,38). In two phase I, pharmacokinetic studies (7,8), i.p.…”

Section: Discussionmentioning

confidence: 99%

Sequential Intraperitoneal Topotecan and Oral Etoposide Chemotherapy in Recurrent Platinum-Resistant Ovarian Carcinoma

Sood¹,

Lush

Geisler

et al. 2004

Clinical Cancer Research

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Purpose:The purpose is to investigate the safety and efficacy of i.p. topotecan and oral etoposide as salvage treatment for patients with platinum-resistant ovarian or primary peritoneal cancer.Experimental Design: Patients were treated with i.p. topotecan initial dose, 1 mg/m 2 on days 1 to 5, followed by oral etoposide 100 mg on days 6 to 9 of a 28-day cycle for six cycles. Dose reduction of topotecan was used for severe bone marrow suppression. Peritoneal (topotecan) and plasma (topotecan and etoposide) levels were assessed at multiple time points using high-pressure liquid chromatography.Results: Twenty-two patients (mean age, 61 years) with a median of 1.5 prior treatments were enrolled. Etoposide peak plasma concentrations ranged from 1.9 to 6.9 g/mL (mean, 3.6 g/mL). Topotecan plasma levels rose with increasing peritoneal concentration and were detectable within 1 hour but tended to decrease rapidly to below detectable levels within 24 hours. The peak plasma concentration of topotecan was 12.82 ؎ 8.55 g/mL with a plasma half-life of 6.17 ؎ 2.75 hours. A total of 104 cycles was administered; 14 patients (64%) completed all six planned cycles. All patients were evaluable for toxicity, and 21 patients were evaluable for response. The most common grade 4 toxicities were neutropenia and thrombocytopenia in eight and four patients (36 and 18%), respectively. There were no treatment-related deaths. The overall response rate was 38% [complete response, three (14%); partial response, five (24%)]. Seven patients had stable disease and six progressed while on treatment.Conclusions: The combination of i.p. topotecan and oral etoposide is an active and well-tolerated regimen in platinumresistant ovarian carcinoma. Additional studies investigating topotecan in combination with etoposide are warranted.

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Alternate Dosing Schedules for Topotecan in the Treatment of Recurrent Ovarian Cancer

Cited by 10 publications

References 11 publications

Topotecan Dosing Guidelines in Ovarian Cancer: Reduction and Management of Hematologic Toxicity

Topotecan Dosing Guidelines in Ovarian Cancer: Reduction and Management of Hematologic Toxicity

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

Sequential Intraperitoneal Topotecan and Oral Etoposide Chemotherapy in Recurrent Platinum-Resistant Ovarian Carcinoma

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