Faculty Opinions recommendation of Early versus delayed treatment of relapsed ovarian cancer (MRC OV05/EORTC 55955): a randomised trial.

Purpose Standard therapy for advanced ovarian cancer consists of a platinum agent in combination with a taxane, which has a 5-year survival rate of approximately 45%. The large individual variability for ovarian cancer patients in both outcome and toxicity risk from chemotherapy makes the identification of pharmacogenetic markers that can be used to screen patients before therapy selection an attractive prospect. Patients and Methods We assessed 27 selected polymorphisms based on previously described associations or putative functional effects in 16 key genes from pathways that may influence cellular sensitivity to taxanes (ABCB1, ABCC1, ABCC2, ABCG2, CDKN1A, CYP1B1, CYP2C8, CYP3A4, CYP3A5, MAPT, and TP53) and platinum (ABCC2, ABCG2, ERCC1, ERCC2, GSTP1, MPO, and XRCC1) using polymerase chain reaction and Pyrosequencing in 914 ovarian cancer patients from the Scottish Randomised Trial in Ovarian Cancer phase III trial who were treated at presentation with carboplatin and taxane regimens after cytoreductive surgery. Results No reproducible significant associations between genotype and outcome or toxicity were found for any of the genes analyzed. Previously reported genotype associations could not be replicated in this large study of a well-defined patient population within one specific clinical trial. Conclusion There are no clear candidates for taxane/platinum pharmacogenetic markers. This study highlights the need for validation of putative genetic markers in large, well-defined clinical sample sets.

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Combretastatin A-4 phosphate (CA4P) carboplatin and paclitaxel in patients with platinum-resistant ovarian cancer: Final phase II trial results

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.5502 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 5502-5502 ◽

Cited By ~ 3

Author(s):

M. Zweifel ◽

G. Jayson ◽

N. Reed ◽

R. Osborne ◽

B. Hassan ◽

...

Keyword(s):

Ovarian Cancer ◽

Phase Ii ◽

Response Rate ◽

Phase Ii Trial ◽

Randomised Trial ◽

Full Data ◽

Vascular Disrupting Agent ◽

Platinum Resistant ◽

Grade 3 ◽

Start Trial

5502 Background: CA4P is a vascular disrupting agent that in pre-clinical models can increase the efficacy of a variety of therapies. A dose escalation trial of CA4P given prior to carboplatin, paclitaxel or both showed the combination was well tolerated and responses were seen in several tumor types including 6/17 with relapsed ovarian cancer. The trial was therefore extended into a phase II trial in patients with platinum resistant ovarian cancer. Methods: Patients with ovarian cancer that had relapsed and could start trial therapy within 6 months of their last platinum chemotherapy were given CA4P 63mg/m2 18–20 hours prior to paclitaxel 175mg/m2 and carboplatin AUC 5 repeated 3 weekly. If > 2 responses were seen in first 18 patients 43 patients were to be treated to confirm response rate>19%. Results: Five of the first 18 patients responded so the study was extended and closed after 44 patients were recruited, with full data available to date on 34. Weekly blood counts have demonstrated grade 3/4 neutropenia in 11 and thrombocytopenia in only 1 patient. Other grade > 2 toxicity seen in > 1 patient was fatigue, nausea / vomiting, pain, alopecia, rapidly reversible ataxia, diarrhoea, neuropathy and was little different to what would be expected with paclitaxel and carboplatin. Hypertension is the commonest CA4P related toxicity and was easily controlled by GTN, then prophylactic amlodipine. Responses according to GCIG criteria, have been seen in 11/34 (32%) patients with an additional unconfirmed PR. Conclusions: The addition of CA4P to paclitaxel and carboplatin is well tolerated and appears to produce a higher response rate in this patient population than if the chemotherapy was given without CA4P. A planned randomised trial will hopefully confirm this. [Table: see text]

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