A phase II study of irinotecan plus cisplatin for patients with advanced stage IIIB or IV NSCLC previously treated with nonplatinum‐based chemotherapy

Kim, Heung T.; Han, Ji‐Youn; Lee, Dae H.; Chun, June Young; Lee, Hong G.; Lee, Jae J.; Kim, Hyae Y.; Lee, Sung Y.; Lee, Jin S.

doi:10.1002/cncr.22063

Cited by 6 publications

(1 citation statement)

References 14 publications

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“…Human clinical studies have shown that combination treatment with irinotecan and cisplatin is efficacious in a wide range of cancer types including SCLC (9)(10)(11)(24)(25)(26), NSCLC (27)(28)(29), ovarian cancer (30), upper gastrointestinal cancers (31)(32)(33)(34)(35), and other less prevalent tumor types (36)(37)(38). Based on phase III randomized trials, this combination remains a prospective treatment for extensive-stage SCLC, with response and survival end points comparable to that of etoposide/cisplatin in the presence of reduced myelosupression.…”

Section: Discussionmentioning

confidence: 99%

Drug ratio–dependent antitumor activity of irinotecan and cisplatin combinations in vitro and in vivo

Tardi

Santos

Harasym

et al. 2009

Molecular Cancer Therapeutics

104

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Irinotecan and cisplatin are two established anticancer drugs, which together constitute an effective combination for treating small-cell lung cancer. We investigated whether the efficacy of this combination could be improved by controlling drug ratios following in vivo administration. Irinotecan and cisplatin combinations were evaluated systematically for drug ratio-dependent synergy in vitro using a panel of 20 tumor cell lines. In vitro screening informatics on drug ratio-dependent cytotoxicity identified a consistently antagonistic region between irinotecan/cisplatin molar ratios of 1:2 to 4:1, which was bordered by two synergistic regions. Liposomal co-formulations of these two agents were developed that exhibited plasma drug half-lives of 6 hours and maintained a fixed drug ratio for more than 24 hours. Drug ratio-dependent antitumor activity was shown in vivo for these liposome formulations, and irinotecan/cisplatin ratios between 5:1 and 10:1 were identified as therapeutically optimal. The relationship between irinotecan/cisplatin ratio and in vivo efficacy was consistent with in vitro drug ratio dependency results. Superior antitumor activity was observed for the liposome-encapsulated 7:1 molar ratio of irinotecan/cisplatin (designated CPX-571) compared with the free-drug cocktail in all models tested. Further efficacy studies in a range of human tumor xenografts, including an irinotecanresistant model, showed that both liposomal agents contributed to the overall efficacy in a manner consistent with in vivo synergy. These results show the ability of drug delivery technology to enhance the therapeutic activity of irinotecan/cisplatin combination treatment by maintaining synergistic ratios in vivo. CPX-571, a fixed-ratio formulation of irinotecan and cisplatin, is a promising candidate for clinical development.

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Section: Discussionmentioning

confidence: 99%

Drug ratio–dependent antitumor activity of irinotecan and cisplatin combinations in vitro and in vivo

Tardi

Santos

Harasym

et al. 2009

Molecular Cancer Therapeutics

104

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Efficacy and safety of first‐ or second‐line irinotecan, cisplatin, and mitomycin in mesothelioma

Fennell

Steele

Shamash

et al. 2006

Cancer

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Morphogenesis of the mammalian forebrain is influenced by the patterning activity of signals emanating from the anterior mesendoderm. In this study, we show that procollagen IIA (IIA), an isoform of the cartilage extracellular matrix protein encoded by an alternatively spliced transcript of Col2a1, is expressed in the prechordal plate and the anterior definitive endoderm. In the absence of IIA activity, the null mutants displayed a partially penetrant phenotype of loss of head tissues, holoprosencephaly, and loss of mid‐facial structures, which is associated with reduced sonic hedgehog (Shh) expression in the prechordal mesoderm. Genetic interaction studies reveal that IIA function in forebrain and face development does not involve bone morphogenetic protein receptor 1A (BMPR1A)‐ or NODAL‐mediated signaling activity. Developmental Dynamics 239:2319–2329. © 2010 Wiley‐Liss, Inc.

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Phase II trial of irinotecan plus cisplatin in patients with recurrent or metastatic squamous carcinoma of the head and neck

Gilbert

Cmelak

Shyr

et al. 2008

Cancer

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BACKGROUND.Patients with recurrent or metastatic HNC have a poor response and survival with currently available chemotherapy agents. Thus, new agents are needed. The authors report the results of a phase II trial of irinotecan and cisplatin in patients with metastatic or recurrent HNC.METHODS.Patients were treated with irinotecan 65 mg/m2 IV over 90 minutes and cisplatin 30 mg/m2 were administered intravenously weekly for four weeks, followed by a two week rest. However, after 17 patients were treated with weekly irinotecan at a dose of 65 mg/m2, toxicity analysis demonstrated the poor tolerance of that dose in this patient population. Thus, the protocol was amended, and irinotecan was dose reduced to a starting dose of 50 mg/m2. Twenty‐three additional patients were treated with this dose.RESULTS.Forty patients were enrolled on study between February 2002 and April 2006, 17 patients at the first dose level and 23 patients at the amended dose level. Overall, 12 of 17 patients (71%) treated with irinotecan 65 mg/m2 experienced clinically significant grade 3 or 4 toxicity. Twelve patients required dose reductions. Toxicity was reduced but 17% of patients still experienced grade 3 or 4 toxicity on the lower irinotecan dose. The response rate was 35% for patients treated at irinotecan 65 mg/m2 and 22% for patients treated at 50 mg/m2. No complete responses were noted.CONCLUSIONS.The combination of irinotecan and cisplatin is efficacious in a poor prognosis group of patients but toxicity is substantial. Cancer 2008. © 2008 American Cancer Society.

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A phase II study of irinotecan plus cisplatin for patients with advanced stage IIIB or IV NSCLC previously treated with nonplatinum‐based chemotherapy

Cited by 6 publications

References 14 publications

Drug ratio–dependent antitumor activity of irinotecan and cisplatin combinations in vitro and in vivo

Drug ratio–dependent antitumor activity of irinotecan and cisplatin combinations in vitro and in vivo

Efficacy and safety of first‐ or second‐line irinotecan, cisplatin, and mitomycin in mesothelioma

Phase II trial of irinotecan plus cisplatin in patients with recurrent or metastatic squamous carcinoma of the head and neck

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