Abstract
e19009 Background: NP has shown anti-tumor activity in MM in a phase II trial. The objective of this study was to determine MTD of NP as part of BCT, consisted of cisplatin (C), temozolomide (T), interleukin-2 (IL2) and interferon-alpha (IFN). Secondary objectives were to evaluate the anti-tumor activity of this combination in MM, and its benefit in preventing central nervous system (CNS) metastasis (mets). Methods: Previously untreated MM patients evaluable by RECIST 1.0 with no history of CNS mets between the ages of 18 and 65 and with ECOG 0-1 were enrolled. NP was given intravenously (IV) on Day (d) 1 and 5 of each cycle. The starting dose on d1 was 100 mg/ m2, and the dose on d5 was 70 mg/ m2, if toxicities permitted. The remainder of the regimen consisted of IV C 20 mg/ m2 daily d1-4, oral T 250 mg/ m2 d1-3, 9 million international units (MIU)/m2 of IL2 via continuous IV infusion for 96 hours, and IFN 5 MIU/m2 via subcutaneous injection d1-5. Treatment was repeated in cycles of 21 d to a maximum of 6 cycles. Prophylactic hematologic growth factors were not allowed in the first cycle. A standard 3+3 escalation method was used for NP d1 dose. Results: Ten pts were enrolled and evaluable for toxicities. Five completed six courses. Because 2 of 5 pts at the starting dose level had dose-limiting toxicities (DLTs) (diarrhea; transaminasemia-TA), the next cohort received d1 NP dose of 80mg/m2. Two of 5 pts at that dose level had DLTs (TA; neutropenia). Overall, the day 5 dose was omitted in 3 patients post third cycle due to thrombocytopenia (TP). There was no grade 5 toxicity. Common grade 3 and 4 toxicities were leucopenia, neutropenia, lymphopenia, anemia, TP, hyponatremia, diarrhea, skin rash, infection, tinnitus, neuropathy and TA. Five of 9 evaluable pts had partial response (PR). The median time-to-progression was 5.3 months (m). The median overall survival was 8.73 m. Six pts developed CNS mets with an overall median time of 5.33 m from treatment start. Conclusions: Additional studies are needed to determine the optimal dosing and schedule of NP as a part of BCT. Despite significant antitumor activity on sites outside the CNS, this combination therapy did not prevent the development of CNS mets.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
