Irinotecan (I), carboplatin (C), and radiotherapy (RT) followed by maintenance bevacizumab (B) in the treatment (tx) of limited-stage small cell lung cancer (LS-SCLC): Update of a phase II trial of the Minnie Pearl Cancer Research Network

Abstract

7085 Background: Targeting VEGF has proven to be an effective tx strategy in many solid tumors including non-small cell lung cancer. VEGF expression in SCLC provides rationale for studying B in addition to chemoradiotherapy. Methods: The endpoints of this multicenter community-based study were to assess the safety, response rate (RR), and progression-free survival (PFS) of I/C/RT followed by B in patients (pts) with LS-SCLC. Tx included: C AUC = 5 IV D1, I 50mg/m2 IV D1,8 Q 21D x 4 cycles, and RT 1.8 Gy daily to a total of 61.2 Gy, beginning with the 3rd cycle. 3rd and 4th cycles were 28D each. Pts were restaged after 4 cycles. If no progressive disease (PD) pts received B 10 mg/kg IV Q 14D x 10 doses. Eligibility included: measurable disease, ECOG PS 0–1, informed consent, and no new brain metastases or bleeding. Results: Fifty-seven pts were enrolled from 8/03 to 10/04. Forty-five pts (79%) and 41 pts (72%) received planned tx with I/C/RT and B, respectively. The range of follow-up is 14–28 months. Baseline features: median age 65 years (42–80); male/female, 37%/63%; ECOG PS 0,1: 26%/74%. Grade (G) 3/4 non-hematologic toxicity: diarrhea (9%), DVT (4%), vomiting (11%), and fatigue (9%). G3/4 hematologic toxicity: neutropenia (37%), anemia (5%), and thrombocytopenia (13%). Only 9% of pts experienced G3/4 toxicity during B tx (1 pt each: DVT, hypokalemia, depression, pain, and colon perforation). There were 2 tx-related deaths (both from respiratory failure; 1 and 2 doses of B had been administered). Complete/partial responses were observed in 15 pts (26%)/31 pts (54%), respectively, for an overall RR of 80% (95% CI 70%-90%). Four pts had stable disease, and 5% had PD (4 pts were unevaluable.) 1- and 2-year PFS rates were 63% and 54%, respectively. 1- and 2- year overall survival (OS) rates were 71% and 29%, respectively. Median OS was 15 months. Conclusions: The safety, RR, and 1- and 2-year survival results of I/C/RT followed by B compare favorably with standard tx for LS-SCLC; and B may improve PFS. Assessing the role of B as maintenance tx in improving OS in this setting will require randomized trials. [Table: see text]

A phase II study of Endostatin in combination with paclitaxel, carboplatin, and radiotherapy in patients with unresectable locally advanced non-small cell lung cancer

“…However, our current data showed that it was difficult to ascertain whether addition of endostatin was efficacious in treating these patients and whether there was a synergy of endostatin plus radiation therapy. The median PFS and OS estimated at 10 and 14 months, respectively, were similar to those of previous clinical trials of CRT alone [ 1 , 2 , 4 – 6 , 10 , 16 ]. Whether the inconsistent schedule of endostatin from other studies made our work unsuccessful is worthy of more research.…”

“…However, endostatin has toxicity concerns and may cause development of tracheoesophageal/bronchial fistulae in NSCLC patients, but this is generally an uncommon event resulting from CRT of lung cancer. In a simultaneous and ongoing study in limited stage SCLC, among 29 patients there were 2 confirmed and 1 suspected episode of tracheoesophageal/bronchial fistulae [ 16 , 17 ]. All 3 patients had grade III esophagitis during CRT and bevacizumab treatment (another tumor angiogenesis inhibitor that is a humanized monoclonal antibody directed against VEGF).…”

Phase II Trial of Irinotecan, Carboplatin, and Bevacizumab in the Treatment of Patients with Extensive-Stage Small-Cell Lung Cancer

“…3,4,14,20,21 The recent success of adding bevacizumab to standard chemotherapy regimens in several solid tumor settings (colorectal, non-small cell lung, and breast) has encouraged the development of bevacizumab in other treatment settings, including SCLC. [5][6][7]11 The role of angiogenesis in SCLC is unknown, although some preclinical models suggest this may be a useful target. 8 -10 Our center previously conducted a phase II study using bevacizumab in a maintenance role, but found little benefit for this strategy.…”

“…8 -10 Our center previously conducted a phase II study using bevacizumab in a maintenance role, but found little benefit for this strategy. 11 Other centers have similarly found no benefit to a maintenance strategy using the angiogenesis inhibitors thalidomide or vandetanib. 22,23 The present trial was planned to introduce bevacizumab earlier in treatment by administering it concurrently with chemotherapy.…”

“…8 -10 We previously completed a phase II trial in patients with limited-stage SCLC using bevacizumab as maintenance therapy following primary treatment with carboplatin, irinotecan, and concurrent radiation. 11 Previous studies by our center and others have shown carboplatin and irinotecan to be well tolerated and active in SCLC. [12][13][14][15][16] In the limited-stage trial, bevacizumab did not seem to add benefit when used as a single agent following combination therapy.…”