Phase II study of maintenance sunitinib following irinotecan and carboplatin as first-line treatment for patients with extensive-stage small-cell lung cancer

Spigel, David R.; Greco, F. Anthony; Rubin, Mark; Shipley, Dianna; Thompson, Dana S.; Lubiner, Eric T.; Eakle, Janice F.; Quinn, Raven; Burris, Howard A.; Hainsworth, John D.

doi:10.1016/j.lungcan.2012.03.009

Cited by 31 publications

(27 citation statements)

References 42 publications

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“…CPT-11 is most frequently used in first-and second-line treatment of metastatic colon cancers, typically in combination with other agents (Smith et al, 2006;Kambe et al, 2012). More recently, CPT-11 has been employed in preclinical and clinical trials against a range of other neoplasticities, including brain tumors, lung, breast, gastric, pancreatic, and gynecologic cancers (Matsumura et al, 2010;Han et al, 2012;Jo et al, 2012;Kim et al, 2012;Spigel et al, 2012;Zaniboni et al, 2012;Lee et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Molecular Insights into Microbialβ-Glucuronidase Inhibition to Abrogate CPT-11 Toxicity

et al. 2013

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Bacterial b-glucuronidases expressed by the symbiotic intestinal microbiota appear to play important roles in druginduced epithelial cell toxicity in the gastrointestinal (GI) tract. For the anticancer drug CPT-11 (irinotecan) and the nonsteroidal anti-inflammatory drug diclofenac, it has been shown that removal of the glucuronide moieties from drug metabolites by bacterial b-glucuronidases in the GI lumen can significantly damage the intestinal epithelium. Furthermore, selective disruption of bacterial b-glucuronidases by small molecule inhibitors alleviates these side effects, which, for CPT-11 {7-ethyl-10-[4-(1-piperidino)-1-piperidino]}, can be dose limiting. Here we characterize novel microbial b-glucuronidase inhibitors that inhibit Escherichia coli b-glucuronidase in vitro with K i values between 180 nM and 2 mM, and disrupt the enzyme in E. coli cells, with EC 50 values as low as 300 nM. All compounds are selective for E. coli b-glucuronidase without inhibiting purified mammalian b-glucuronidase, and they do not impact the survival of either bacterial or mammalian cells. The 2.8 Å resolution crystal structure of one inhibitor bound to E. coli b-glucuronidase demonstrates that it contacts and orders only a portion of the "bacterial loop" present in microbial, but not mammalian, b-glucuronidases. The most potent compound examined in this group was found to protect mice against CPT-11-induced diarrhea. Taken together, these data advance our understanding of the chemical and structural basis of selective microbial b-glucuronidase inhibition, which may improve human drug efficacy and toxicity.

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Section: Introductionmentioning

confidence: 99%

Molecular Insights into Microbialβ-Glucuronidase Inhibition to Abrogate CPT-11 Toxicity

et al. 2013

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“…In another phase II maintenance trial by Spigel et al (53), 34 eligible patients with extensive stage SCLC were treated with carboplatin plus weekly irinotecan. Patients who achieved disease control were treated with sunitinib 25 mg daily until disease progression or unacceptable toxicity.…”

Section: Sunitinibmentioning

confidence: 99%

Targeting angiogenesis in small cell lung cancer

Stratigos

Matikas

Voutsina

et al. 2016

Transl. Lung Cancer Res.

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Small cell lung cancer (SCLC) is a highly aggressive and lethal malignancy. Despite high initial response rates to systemic chemotherapy, the disease eventually relapses; further treatment only modestly improves outcomes and overall survival (OS) for patients with extensive stage disease is less than one year.Little progress has been made during the past decades, with no new drugs approved. Consequently, the development of novel strategies is an unmet need. The inhibition of angiogenesis, a defining characteristic of cancer, has demonstrated modest efficacy in several human malignancies, including non-small cell lung cancer (NSCLC). However, results from clinical trials in SCLC have been disappointing, and no anti-angiogenic agent has received regulatory approval due to lack of clinical efficacy. The elucidation of underlying mechanisms responsible for tumor resistance to angiogenic therapy and the simultaneous blockade of multiple elements that play a role in angiogenesis need to be further explored.

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“…The studies reviewed reported grade 3 or 4 diarrhea in 2% to 23% of patients. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][16][17][18][19] D. Hematopoietic Growth Factors: Accepted practice guidelines and pharmaco-economic analysis suggest that an antineoplastic regimen have a greater than 20% incidence of febrile neutropenia before prophylactic use of colony stimulating factors (CSFs) is warranted. For regimens with an incidence of febrile neutropenia between 10% and 20%, use of CSFs should be considered.…”

Section: Supportive Care a Acute And Delayed Emesis Prophylaxis: The Icmentioning

confidence: 99%

“…For regimens with an incidence of febrile neutropenia less than 10%, routine prophylactic use of CSFs is not recommended. 40,41 In the IC trials reviewed, febrile neutropenia was reported in 1% to 19% of patients 1,2,4,8,9,13,16,18,19 ; severe neutropenia (grade 3 or 4) was reported in 2% to 55% of patients. 2 43,44 There was one treatment-related death due to anaphylactic shock after IV administration of carboplatin 17 and several reports of allergic reactions (grade 1-2) 1% to 4% 10 and rash (grade 1-2) 2% 16 in the studies reviewed.…”

Section: Supportive Care a Acute And Delayed Emesis Prophylaxis: The Icmentioning

confidence: 99%

Irinotecan and Carboplatin (IC) Regimen for Small-Cell Lung Cancer and Non-Small-Cell Lung Cancer

Rutledge

Waddell²,

Solimando³

2014

Hosp Pharm

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The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc., 4201 Wilson Blvd #110-545, Arlington, VA 22203, e-mail: OncRxSvc@comcast.net; or J. Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net.

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Phase II study of maintenance sunitinib following irinotecan and carboplatin as first-line treatment for patients with extensive-stage small-cell lung cancer

Cited by 31 publications

References 42 publications

Molecular Insights into Microbialβ-Glucuronidase Inhibition to Abrogate CPT-11 Toxicity

Molecular Insights into Microbialβ-Glucuronidase Inhibition to Abrogate CPT-11 Toxicity

Targeting angiogenesis in small cell lung cancer

Irinotecan and Carboplatin (IC) Regimen for Small-Cell Lung Cancer and Non-Small-Cell Lung Cancer

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