Combination of paclitaxel and carboplatin as second‐line therapy for patients with metastatic melanoma

Rao, Ravi A.; Holtan, Shernan G.; Ingle, James N.; Croghan, Gary A.; Kottschade, Lisa A.; Creagan, Edward T.; Kaur, Judith S.; Pitot, Henry C.; Markovic, Svetomir N.

doi:10.1002/cncr.21611

Cited by 107 publications

(65 citation statements)

References 85 publications

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“…In some patients, taxanes were associated with prolonged duration of disease control. Higher response rates were seen (12 -41%) when taxanes were given in association with other anticancer agents, such as temozolomide, dacarbazine, cisplatin, carboplatin, or tamoxifen (10,11).…”

Section: Introductionmentioning

confidence: 99%

Docetaxel-induced apoptosis in melanoma cells is dependent on activation of caspase-2

Mhaidat

Wang

Kiejda

et al. 2007

Molecular Cancer Therapeutics

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Section: Introductionmentioning

confidence: 99%

Docetaxel-induced apoptosis in melanoma cells is dependent on activation of caspase-2

Mhaidat

Wang

Kiejda

et al. 2007

Molecular Cancer Therapeutics

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“…Combining carboplatin and paclitaxel did not appear to provide additional benefits with overall response rate of <10% and 17% in two Cancer Therapy: Clinical Authors' Affiliations: 1 prospective trials with small cohorts (21,22). In a retrospective analysis, 26% of patients with advanced melanoma treated with a carboplatin-paclitaxel combination had partial response (23).…”

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confidence: 99%

A Phase I Trial of the Oral, Multikinase Inhibitor Sorafenib in Combination with Carboplatin and Paclitaxel

Flaherty

Schiller

Schuchter

et al. 2008

Clinical Cancer Research

130

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Purpose: This study evaluated the safety, maximum tolerated dose, pharmacokinetics, and antitumor activity of sorafenib, a multikinase inhibitor, combined with paclitaxel and carboplatin in patients with solid tumors. Patients and Methods: Thirty-nine patients with advanced cancer (24 with melanoma) received oral sorafenib 100, 200, or 400 mg twice daily on days 2 to 19 of a 21-day cycle. All patients received carboplatin corresponding to AUC6 and 225 mg/m 2 paclitaxel on day 1. Pharmacokinetic analyses were done for sorafenib on days 2 and 19 of cycle 1and for paclitaxel on day 1of cycles 1and 2. Pretreatment tumor samples from 17 melanoma patients were analyzed for BRAF mutations. Results: Sorafenib was well tolerated at the doses evaluated. The most frequent severe adverse events were hematologic toxicities (grade 3 or 4 in 33 patients, 85%). Twenty-seven (69%) patients had sorafenib-related adverse events, the most frequent of which were dermatologic events (26 patients, 67%). Exposure to paclitaxel was not altered by intervening treatment with sorafenib. Treatment with sorafenib, paclitaxel, and carboplatin resulted in one complete response and nine partial responses, all among patients with melanoma. There was no correlation between BRAF mutational status and treatment responses in patients with melanoma. Conclusions:The recommended phase II doses are oral 400 mg twice daily sorafenib, carboplatin at an AUC6 dose, and 225 mg/m 2 paclitaxel. The tumor responses observed with this combined regimen in patients with melanoma warrant further investigation.

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“…Although it remains to be determined in appropriately controlled trials in patients with melanoma whether combination therapies with sorafenib show superior efficacy to chemotherapy alone, sorafenib has shown almost double the clinical benefit of historical controls of carboplatin/ paclitaxel alone in second-line melanoma patients (85% versus 45%; refs. 24,25). Whether this effect is mediated through inhibition of the Raf kinase pathway, rather than inhibition of angiogenesis, is also presently unclear.…”

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confidence: 99%

Phase I Trial of Sorafenib in Combination with IFN α-2a in Patients with Unresectable and/or Metastatic Renal Cell Carcinoma or Malignant Melanoma

Escudier

Lassau

Angevin

et al. 2007

Clinical Cancer Research

135

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Purpose: To determine the safety, maximum tolerated dose, pharmacokinetics, and efficacy, and to evaluate biomarkers, of the multikinase inhibitor sorafenib plus IFN a-2a in advanced renal cell carcinoma (RCC) or melanoma. Experimental Design: Patients received 28-day cycles of continuous, oral sorafenib twice daily and s.c. IFN thrice weekly: sorafenib 200 mg twice daily plus IFN 6 million IU (MIU) thrice weekly (cohort1); and sorafenib 400 mg twice daily plus IFN 6 MIU thrice weekly (cohort 2); or plus IFN 9 MIU thrice weekly (cohort 3). Tumor response was assessed by Response Evaluation Criteria in Solid Tumors and dynamic contrast-enhanced ultrasonography. Results: Thirteen patients received at least one dose of sorafenib plus IFN (12 RCC; one melanoma). The maximum tolerated dose was not reached [only one dose-limiting toxicity (grade 3 asthenia)]. Most frequently reported drug-related adverse events were grade 2 or less in severity, including fatigue, diarrhea, nausea, alopecia, and hand-foot skin reaction. One (7.7%) RCC patient achieved partial response and eight (61.5%) had stable disease (including the melanoma patient). Good responders assessed by dynamic contrast-enhanced ultrasonography had increased progression-free survival and overall survival, relative to poor responders. IFN had no effect on the pharmacokinetics of sorafenib. There were no significant changes in absolute values of lymphocytes, levels of proangiogenic cytokines, or inhibition of phosphorylated extracellular signalregulated kinase inTcells or natural killer cells, with combination therapy. Conclusions: This sorafenib combination was well tolerated, with preliminary antitumor activity in advanced RCC and melanoma patients. There were no drug-drug interactions and the recommended dose for future studies is sorafenib 400 mg twice daily plus IFN 9 MIU.Renal cell carcinoma (RCC) and melanoma have poor prognoses when diagnosed in advanced stages (1), and are associated with a median survival of V12 months (2, 3). RCC accounts for 80% to 95% of kidney tumors, and f30% of RCC patients have metastatic disease at diagnosis (1, 4, 5).The Raf/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK signaling pathway, which regulates cell proliferation and survival (6), is implicated in the onset and development of RCC (7) and melanoma (6). Overactivation of Raf-1 is detected in 55% of RCC biopsies in the absence of oncogenic ras/raf mutations (7). Clear cell carcinomas, which account for 75% to 85% of renal tumors, are characterized by loss of the von Hippel-Lindau tumor-suppressor gene (8), leading to overexpression of proangiogenic vascular endothelial growth factor (VEGF) and platelet-derived growth factor-h (9, 10). Activating b-raf mutations occur in >60% of melanomas, of which f90% are V600E (11, 12). The V600E b-raf mutant is constitutively active and implicated in tumor development (12). Inhibiting Raf/MEK/ERK signaling induces apoptosis in melanoma cells, but not in normal melanocytes, suggesting that oncogenic b-raf ma...

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Combination of paclitaxel and carboplatin as second‐line therapy for patients with metastatic melanoma

Cited by 107 publications

References 85 publications

Docetaxel-induced apoptosis in melanoma cells is dependent on activation of caspase-2

Docetaxel-induced apoptosis in melanoma cells is dependent on activation of caspase-2

A Phase I Trial of the Oral, Multikinase Inhibitor Sorafenib in Combination with Carboplatin and Paclitaxel

Phase I Trial of Sorafenib in Combination with IFN α-2a in Patients with Unresectable and/or Metastatic Renal Cell Carcinoma or Malignant Melanoma

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