Paclitaxel/Carboplatin/Etoposide (Pce) Therapy For Advanced Poorly Differentiated Neuroendocrine (Pdne) Carcinoma: A Minnie Pearl Cancer Research Network Phase Ii Trial.

4058 Background: PDNE carcinoma may arise from a variety of primary sites or present as an unknown primary. PDNE tumors have historically been sensitive to platinum/etoposide-based chemotherapy, as opposed to very poor activity in well differentiated neuroendocrine tumors. This phase II trial expands our experience with PCE in the treatment of patients (pts) with PDNE carcinoma. The objectives were to determine the objective response rate and survival. Methods: Eligibility requirements: small cell carcinoma (except small cell lung cancer) or poorly differentiated carcinoma (PDC) with diagnostic IP staining or electron microscopy; unknown or known primary; metastatic or locally advanced tumor; well differentiated carcinoid-type tumors excluded; ECOG PS 0–2; no previous chemotherapy; measurable disease; adequate organ function; informed consent. Pts received P 200mg/m2 IV, day 1; C AUC 6.0 IV, day 1; E 50/100mg po alternating, days 1–10; (repeated q 21 days x 4 courses). Local radiotherapy was subsequently administered to patients with advanced local tumor. Responding/stable pts received P 70mg/m2 IV, 6 of 8 weeks, for 24 weeks. Results: Between 1/99 and 11/04, 66 pts were treated. Pt characteristics: median age 58 years; male/female, 40/26 [small cell (12 pts); PDC (54 pts)]; primary site known/unknown, 27/39; visceral metastases, 51 pts (77%); ≥ 2 metastatic sites, 44 pts (66%). 59 pts were evaluable for response: complete, 9 pts (15%); partial, 24 pts (40%); stable/minor, 21 pts (35%); progression, 5 pts (10%). Median response duration was 9 months. After a median follow-up of 32 months, median survival is 14.8 months, with 1-, 2-, 3-, 4-, and 5-year survivals of 57%, 34%, 23%, 15%, and 15%, respectively. There was no difference (p=0.43 log rank) in survival comparing pts with known to unknown primary (median 15.6 vs. 13.8 and 1-, 2-year survivals 58%, 39% vs. 55%, 30%, respectively). Grade 3/4 toxicity was predominantly myelosuppression. Conclusions: PCE is active against PDNE and produces clinical benefit and prolongation of survival. A minority of pts remain alive, some progression-free, for several years. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb