Table 1. Agents that have undergone testing in small cell lung cancer.
| Agent (Ref.) | Mechanism of action | Study design | Result |
|---|---|---|---|
| Interferon-alfa (106-109) | Immunomodulator | Phase 3 (multiple) | Two studies with improved survival in limited-stage patients, two studies with no survival benefit |
| Interferon-gamma (110, 111) | Immunomodulator | Phase 3 (multiple) | No improvement in survival |
| Interleukin-2 (112) | Immunomodulator | Phase 2 | 21% response rate but excessive toxicity |
| Ipilimumab (104) | Humanized anti-CTLA4 antibody | Randomized Phase 2 | Improved immune-related PFS when administered with carboplatin/paclitaxel in phased dosing schedule in chemo-naïve extensive stage SCLC |
| Marimastat (113) | Matrix metalloproteinase inhibitor | Phase 3 | No improvement in progression-free or overall survival |
| Tanomastat (114) | Matrix metalloproteinae inhibitor | Phase 3 | No improvement in progression-free or overall survival |
| Imatinib (115-117) | c-kit tyrosine kinase inhibitor | Phase 2 (multiple) | No responses |
| Temsirolimus (118) | Mammalian target of rapamycin (mTOR) inhibitor | Randomized Phase 2 | Higher dose level demonstrated improved survival compared to lower dose level when given post-first line therapy; both doses showed improvement in outcome compared with historical control |
| Everolimus (119) | Mammalian target of rapamycin (mTOR) inhibitor | Phase 2 | Limited anti-tumor activity in relapsed SCLC. |
| Tipifarnib (120) | Farnesyl transferase inhibitor | Phase 2 | No responses |
| Cixutumumab (83) | Monoclonal IGF-1R antibody | Randomized Phase 2 | No improvement in progression free survival when added to cisplatin/etoposide in chemo-naïve extensive stage SCLC |
| Vismodegib (83) | Hedgehog pathway inhibitor | Randomized Phase 2 | No improvement in progression free survival when added to cisplatin/etoposide in chemo-naïve extensive stage SCLC |
| Oblimersen (121) | Bcl-2 antisense | Randomized Phase 2 | No improvement in response rate |
| Navitoclax (122) | Bcl-2 and bcl-xL inhibitor | Phase 2 | Limited activity in recurrent and progressive disease |
| Obatoclax mesylate (123, 124) | BH3-mimetic exhibits binding affinity for bcl-2 family members, including bcl-2, bcl-XL, and mcl-1 | Phase 2 | No increased response rate when added to topotecan in relapsed SCLC |
| Randomized Phase 2 | Trend toward improved response rate, PFS and OS in chemo-naïve extensive stage SCLC | ||
| Bortezomib (125) | Proteosome inhibitor | Phase 2 | One response in refractory patient (2% overall response rate) |
| BEC-2 + BCG adjuvant (126) | Ganglioside (GD3) anti-idiotype vaccine | Phase 3 | No improvement in progression-free or overall survival |
| Thalidomide (127, 128) | Multiple immunomodulatory effects, also inhibits vascular endothelial growth factor (VEGF) | Phase 3 | Improved survival from 8.7 to 11.7 months but not significant (hazard ratio 0.74; P =.16) |
| Phase 3 | No improvement in any parameters | ||
| Vandetanib (129) | Tyrosine kinase inhibitor of VEGFR-2 and EGFR | Randomized Phase 2 | No improvement in progression-free survival |
| Sorafenib (130) | RAF, VEGFR-2,VEGFR-3, PDGFRα Inhibitor | Phase 2 | 5% response rate in relapsed disease |
| Cediranib(131, 132) | VEGFR-1, VEGFR-2,VEGFR-3, PDGFRβ, c-KIT Inhibitor | Phase 2 | Minimal activity as a single agent in relapsed disease |
| Phase 1 | 8-month progression-free survival with cisplatin and etoposide | ||
| Bevacizumab (133-136) | Monoclonal antibody to VEGF | Phase 2 (multiple) | No increased risk of hemorrhage. Favorable survival compared with historical control. |
| Randomized Phase 2 | Improved progression free survival for bevacizumab, but not in overall survival | ||
| Sunitinib (137) | VEGFR-1, VEGFR-2,VEGFR-3, PDGFRα, PDGFRβ, RET, c-KIT, FLT3 | Phase 3 | Improved progression free survival as maintenance after etoposide/platinum compared to placebo (P = 0.037) |
Reprinted from ref. 138: DeVita VT Jr, Lawrence TS, Rosenberg SA, editors. DeVita, Hellman, and Rosenberg's cancer: principles & practice of oncology. 10th ed. Philadelphia: Wolters Kluwer; 2014.