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A Phase II Study of Velcade, Doxil, and Thalidomide (VDT) in Relapsed/Refractory Myeloma
By Asher A. Chanan-Khan, MD
12.18.06





Patients treated with a median of four prior therapies were given this steroid-free regimen as salvage therapy. There were 22% complete responses, the treatment was very well tolerated, and patients responded regardless of prior therapy.

ABSTRACT:

Final Results of a Phase II Study of Bortezomib (Velcade) in Combination with Liposomal Doxorubicin (Doxil) and Thalidomide (VDT) Demonstrate a Sustained High Response Rates in Patients (pts) with Relapsed (rel) or Refactory (ref) Multiple Myeloma. Session Type: Poster Session, Board #768-III

Asher Alban Chanan-khan, Swaminathan Padmanabhan, Kena C. Miller, Laurie Musiel, Jihnhee Yu, Zale P. Bernstein, Rami Manochakian, Myron S. Czuczman Medicine, Division of Lymphoma/Myeloma, Roswell Park Cancer Institute, Buffalo, NY, USA

Background: Tumor microenvironment (ME) plays an important role in MM. It is associated with disease progression, metastasis, and resistance to therapy. Therefore, targeting the ME and the tumor cell simultaneously may be an effective way to overcome resistance in pts with rel/ref MM.
Aim: Orlowski et al reported improved anti-tumor responses when bortezomib (V) was combined with doxil (D) in pts with hematologic malignancies. We investigated clinically, this approach i.e., targeting the MM cell as well as its ME, using a combination of V, D and low-dose thalidomide (T) as salvage therapy for pts with rel/ref MM. Here we report the final results along with survival data of this phase II study.
Methods: All pts with rel/ref disease were eligible for this study. V was given at 1.3mg/m2 (D1,4,15,18) and D at 20mg/m2 (D1,15) every 4 weeks with daily T (200 mg) for 4-6 cycles. SWOG criterion was used to assess response. Low-dose coumadin (1-2 mg po qd) was used for prevention of venous thromboembolism (VTE).
Results: Twenty three pts (9M, 14F; median age -57 , range 43-79 yrs; 21MM, 2 WM) have been enrolled. All pts had Stage III disease, median b2M was 4.2 and median number of prior therapies were 5(range 1-6). Prior therapies included stem cell transplant(SCT) in (41%), T (41%), adriamycin(A) (65%) steroids (82%) and velcade (12%). 74% had refractory disease. Seventeen pts have completed at least 1 cyc and are available for toxicity and response evaluation. One pt died of sepsis prior to completing 1 cyc and 1 pt with PR was taken off study for non-compliance after 1 cyc. ORR was with 65%(CR+PR) with 23% CR all of whom were IFE negative. The Median Progression Free survival was 10.9 months with an median overall survival of 15.7 months. Toxicity: 2 pts developed Gr. II plantar-palmar erythrodysthesia (PPE) and 1 had Gr. III cellulitis. No VTE was noted. No significant non-hematologic Gr. III/IV toxicity were seen. Despite prior exposure to anthracycle, we did not noted any cardiotoxicity with D.No significant neuropathy was noted.
Conclusions: Pt with rel/ref MM usually have aggressive disease with paucity of effective regimens. VDT is an effective salvage regimen. Final results show high response rates with 22% of the patients achieving complete (IFE-) remissions. Responses were noted regardless of type of prior therapy. VDT could be safely given in patients with renal failure/insufficiency. Venous Thromboembolism (VTE) does not appear to be a problem with low dose coumadin prophylaxis. Final results of this phase II study will be presented at the 48 th annual ASH meeting.
Abstract #3539 appears in Blood, Volume 108, issue 11, November 16, 2006


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