Phase II study of maintenance sunitinib following irinotecan and carboplatin as first-line treatment for patients with extensive-stage small-cell lung cancer☆,☆☆
Introduction
Doublet chemotherapy is standard first-line treatment for patients with extensive-stage small-cell lung cancer (ES-SCLC). Platinum-based doublets are associated with high response rates and early improvement in disease-related symptoms [1], [2], [3], [4], [5], [6], [7], [8]. However, the majority of patients will experience relapse of their disease within the first year, and fewer than 10% of patients will survive beyond 2 years [9]. Newer strategies are needed to prevent disease relapse.
Angiogenesis plays an important role in cancer cell survival and metastasis in many solid tumors including SCLC [10], [11], [12]. Sunitinib is an oral multikinase inhibitor of angiogenesis and cellular proliferation [13]. Sunitinib inhibits several molecular targets including the vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor receptor (PDGFR), Flt-3, and C-kit. Sunitinib is FDA-approved for the treatment of advanced renal cell cancer (RCC) and gastrointestinal stromal tumors (GIST), and has been studied in multiple advanced cancer settings including non-small-cell lung cancer (NSCLC) [14], [15], [16], [17]. Sunitinib has been combined safely with irinotecan-based combinations in patients with advanced colorectal cancer [18] and glioblastoma [19], [20], and with carboplatin and paclitaxel in advanced solid tumors [21].
Platinum/irinotecan doublets have been extensively studied in SCLC including carboplatin and irinotecan [1], [2], [3], [4], [5], [6], [8], [22], [23], [24]. These doublets are equivalent in efficacy to platinum/etoposide regimens, with less myelosuppression, but more severe diarrhea [25], [26], [27], [28], [29]. Herein we report on a multicenter phase II trial where sunitinib was administered as monotherapy following irinotecan and carboplatin in patients with newly diagnosed ES-SCLC.
Section snippets
Patients and methods
This trial was initiated in February 2009. Participating centers included the Sarah Cannon Research Institute and select sites from the Sarah Cannon Oncology Research Consortium, a national community-based research network (see Appendix A). The trial was registered with ClinicalTrials.gov, a service of the NIH (#NCT00695292).
Patient characteristics
Thirty-four patients were enrolled from February 2009 to October 2009, not including the 3 patients who were treated with concurrent sunitinib prior to the modified design. Baseline characteristics for all patients are described in Table 1. The median age was 65 years (range, 41–80 years). Eighteen (53%) patients were male and 16 patients were female. ECOG PS was 0 in 16 (47%) patients and 1 in 18 patients.
Treatment received
The median follow-up is 50 weeks (range, 37–68 weeks). Twenty-one (62%) patients completed 6
Discussion
Despite high response rates and early symptom control with chemotherapy, few patients diagnosed with ES-SCLC will live beyond 2 years. The most recent advance in the care of patients with ES-SCLC was with the use of prophylactic cranial irradiation in patients who had responded to first-line chemotherapy [34]. However, even in this selected group of patients, the 1-year overall survival was less than 30%. Newer approaches in treatment are needed.
Inhibiting angiogenesis has proven to be an
Conflict of interest statement
Eric Lubiner reported stock or ownership interests to disclose with Pfizer. All other authors had none to declare.
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Supported in part by a grant from Pfizer, Inc., New York, NY.
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Preliminary data presented at the American Society of Clinical Oncology Annual Meeting, Chicago, IL, 2010 and the Chicago Multidisciplinary Symposium in Thoracic Oncology, Chicago, IL, 2010.