Evaluation of the incidence of carboplatin hypersensitivity reactions in cancer patients
Marisa A. NavoAnuradha KunthurMartina L. BadellLarry CofferMaurie MarkmanJubilee BrownJudith A. Smith
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Carboplatin
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Recurrent ovarian cancer is a lethal disease, and few patients can be cured. Although most patients receive standardized surgery and chemotherapy, the status of recurrent disease is heterogeneous. The site of recurrence and the survival intervals after recurrence are also widely distributed. Among a number of factors, many clinical trials identified time to recurrence was the factor most related to chemosensitivity at first relapse. The current recommendation for platinum sensitive ovarian cancer is a carboplatin containing combination chemotherapy. Generally, a single agent is chosen for platinum resistant ovarian cancer. Patients with single site recurrence and a long disease free interval are candidates for secondary cytoreduction, which may provide longer survival. There are several treatment choices at first relapse, and disease status, chemotherapy-free interval, and the patient's condition play a major role in the decision making process.
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Abstract: Epithelial ovarian cancer is the most lethal gynaecological malignancy with an estimated 295,414 new cases and 184,799 deaths around the world. Cytoreductive surgery and combination chemotherapy have remained a standard therapy for decades. The majority of women diagnosed with ovarian cancer will receive systemic chemotherapy for recurrent or advanced diseased. In recent years, therapies such as anti-angiogenics, PARP inhibitors, and dose-dense chemotherapy have emerged as novel strategies against ovarian cancer. Dose-dense chemotherapy, usually with a carboplatin and paclitaxel regimen, has been proposed as an alternative to conventional chemotherapy for these patients. However, the results for different trails are inconsistent and dose-dense chemotherapy remains controversial. Results from the JGOG 3016 study showed a progression free survival and overall survival benefit, with increased neurotoxicity and anaemia. While the GOG 262, MITO-7, GOG 252 and ICON8 studies found no benefit on progression free survival, with a recent meta-analysis concluding that three weekly chemotherapy remains the standard of care. Ovarian cancer molecular subtypes and differences in pharmacogenetics between populations may explain the differences in response to dose dense chemotherapy, however our understanding of this factors is still lacking. Here, we reviewed the evidence for and against dose-dense chemotherapy and the possible factors for the different results among trials.
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Recent genetic findings are shedding light on who is at risk for epithelial ovarian cancer, by far the most common of ovarian malignancies. Current screening tests are inadequate, but a serum test of lysophosphatidic acid shows promise. Clinical trials show that cisplatin or carboplatin plus paclitaxel increases progression-free and overall survival times vs regimens that do not contain paclitaxel, and that a carboplatin-paclitaxel regimen is less toxic than cisplatin-paclitaxel and can be given on an outpatient basis. The development of newer cytotoxic drugs and alternative routes of administering chemotherapy offers hope of improved survival for women with advanced ovarian cancer.
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The authors summerize the results of second-line combination chemotherapy with paclitaxel (175 mg/m2, 3h) and carboplatin (AUC 5 mg/ml.min) in patients with recurrent epithelial ovarian cancer. The paclitaxel/carboplatin therapy was applied in 57 patients in 297 courses (median course/patient was 5, range 2, 12). Complete response (CR) was found in 3 patients (3/57 = 5%), however the tumorous process progressed after some time. The median progression free interval (PFI) was found to be 15 (range 3,130) weeks, with an average of 24.3 +/- 26.5 weeks. The authors conclude, that second-line paclitaxel combination therapy produces poorer results than the first-line treatment. These results, which are similar to the literature data have led to the agreement: paclitaxel can be applied in ovarian cancer patients only in first-line chemotherapy in Hungary from the year 2000.
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Development of hypersensitivity reactions to carboplatin (CP) during cancer treatment makes optimal chemotherapy difficult to achieve. Many approaches have previously been used following the development of reactions to CP. We report on a patient with ovarian cancer who developed a hypersensitivity reaction to CP. The patient was successfully treated following replacement of carboplatin with cisplatin.
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