Pazopanib and Weekly Topotecan in Patients Recurrent Ovarian Cancer (TOPAZ) - Full Text View - ClinicalTrials.gov

Pazopanib and Weekly Topotecan in Patients Recurrent Ovarian Cancer (TOPAZ) - Full Text View - ClinicalTrials.gov

abstract: Weekly paclitaxel as a single agent or in combination with carboplatin or weekly topotecan in patients with resistant ovarian cancer: the CARTAXHY randomized phase II trial (GINECO)

Conclusions: Combination chemotherapy in platinum-resistant ROC (recurrent ovarian cancer) was more toxic than weekly paclitaxel and did not significantly prolong PFS.

A weekly topotecan and biweekly bevacizumab combination demonstrates acceptable toxicity and encouraging efficacy in patients with platinum-resistant

Note: pay particular attention to the side effects/adverse events

Markman commentary: Can weekly topotecan substitute for a multi-day regimen in the treatment of ovarian cancer? Sadly, 10 years later the answer remains unknown

Gynecologic Oncology
Article in Press

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doi:10.1016/j.ygyno.2011.04.020 | How to Cite or Link Using DOI Copyright © 2011 Elsevier Inc. All rights reserved.

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Clinical Commentary

Can weekly topotecan substitute for a multi-day regimen in the treatment of ovarian cancer? Sadly, 10 years later the answer remains unknown

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Maurie Markman^a,

^a Cancer Treatment Centers of America, Eastern Regional Medical Center, 1331 East Wyoming Avenue, Philadelphia, PA 19046 USA

Received 28 March 2011; 

accepted 16 April 2011. 

Available online 12 May 2011.

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abstract: Weekly paclitaxel as a single agent or in combination with carboplatin or weekly topotecan in patients with resistant ovarian cancer:

CONCLUSIONS:

Combination chemotherapy in platinum-resistant ROC was more toxic than weekly paclitaxel and did not significantly prolong PFS.

abstract: A phase II study of two topotecan regimens evaluated in recurrent platinum-sensitive ovarian, fallopian tube or primary peritoneal cancer: (GOG 146Q)

Phase 1/pharmacology study of intraperitoneal topotecan alone and with cisplatin: potential for consolidation in ovarian cancer.

Adding topotecan to standard treatment for ovarian cancer does not improve progression-free survival

Blogger's Note: discussions/research have been made in the past regarding triple therapies (irrespective of types of therapies) with most resulting, if not all, leading to increased toxicities/no survival advantage

"...Adding topotecan to carboplatin plus paclitaxel, the standard treatment for ovarian cancer, does not improve progression-free survival in patients and leads to greater toxicity, according to a study published online October 11 in the Journal of the National Cancer Institute.

Cisplatin plus paclitaxel, and carboplatin plus paclitaxel, are the most widely accepted first-line regimens for advanced epithelial ovarian cancer. Still, most women relapse and die from their disease. One possible solution is to add a third agent, such as topotecan, which has activity in the treatment of recurrent disease. However, combining topotecan with carboplatin plus paclitaxel as a triplet therapy is problematic because of bone marrow toxicity. So, to integrate topotecan into the standard regimen researchers tested cisplatin plus topotecan followed by carboplatin plus paclitaxel.

The phase III randomized study included 819 women aged 28-78 with newly-diagnosed stage IIB or more advanced ovarian cancer. The study was led by Paul Hoskins, M.D., of the British Columbia Cancer Agency in Vancouver and colleagues from three other groups: the NCIC Clinical Trials Group at Queen's University in Kingston, Canada, the European Organization for Research and Treatment of Cancer – Gynecologic Cancer Group, European Union, and the Grupo Espańol de Investigación en Cáncer de Ovario in Spain.

The women in the study were from Canada and Europe, and were randomly assigned to one of two study groups: the first arm received cisplatin and topotecan, followed by carboplatin and paclitaxel; the second arm received only carboplatin and paclitaxel...."

2010 Review: Cochrane Collaboration Topotecan for ovarian cancer

Background
Chemotherapeutic agents such as topotecan can be used to treat ovarian cancer. The effects of using topotecan as a therapeutic agent have not been previously been systematically reviewed.
Objectives
To evaluate the effectiveness and safety of topotecan for the treatment of ovarian cancer. 

Results: 

Participants were more likely to respond to topotecan on a 21-day cycle as opposed to a 42-day cycle (RR 7.23, 95% CI 0.94 to 55.36). Small tumor diameter, sensitivity to platinum-based chemotherapy was associated with better prognosis. Small sample size, methodological flaws and poor reporting of the included trials made measurement bias of the trials difficult to assess.

Plain language summary

Topotecan is an active second line chemotherapeutic drug, used to treat patients with relapsed ovarian carcinoma
It appears to have a similar level of effectiveness as paclitaxel and pegylated liposomal doxorubicin, though with different patterns of side effects. Larger, well-designed randomised controlled trials (RCTs) are required to define an optimal regime.

Efficacy of lower dose of weekly topotecan in recurrent epithelial ovarian and primary peritoneal cancer resistant to platinum-based therapy

Conclusions: Lower dose of weekly topotecan was well tolerated in patients with platinum-resistant ovarian or peritoneal cancer at first relapse, with a favourable hematologic profile. Moreover, antitumor activity was similar to that reported for the standard dose of weekly regimen.

Bridging the Gap between Cytotoxic and Biologic Therapy with Metronomic Topotecan and Pazopanib in Ovarian Cancer

"Pazopanib therapy in combination with metronomic topotecan therapy showed significant antitumor and antiangiogenic properties in preclinical ovarian cancer models and warrants further investigation as a novel therapeutic regimen in clinical trials."

A phase I study of weekly temsirolimus and topotecan in the treatment of advanced and/or recurrent gynecologic malignancies