|
|
|
Pegylated Doxorubicin (D), Vincristine (V), Reduced Frequency Dexamethasone (d) and Thalidomide (T) (DVd-T) In Newly Diagnosed (Nmm) and Relapsed/Refractory (Rmm) Multiple Myeloma Patients
DVd is an effective and well-tolerated regimen in newly diagnosed MM pts with a response rate of 88%, yet CR and Near CR (NCR) rates are low at < 20%. In the Rmm pts the overall response rate is 22% and NCR is <5%. DVd significantly reduces the number of abnormal angiogenic activity in the treated patients; however this finding does not impact PFS. T has shown activity in MM pts. Biologically T has a direct anti-myeloma effect in addition to its ability to modulate integrins, rendering the myeloma cell vulnerable and sensitized to different chemotherapeutic agents. T as a single agent or in combination with steroids results in CR+NCR rates of < 20%. We evaluated the role of T in combination with DVd in Nmm Rmm pts with the primary objective of improving the response rate, quality of response and maintain the anti-angiogenic activity achieved with the DVd regimen. SWOG criteria were used to assess response, and NCR was defined as a decrease of the M-Protein by >90%. The regimen was given as follows: on day 1 D was given at 40 mg/ m2 IVPB; V at 2 mg IVP d at 40 mg PO daily X 4 days. T was started at 50 mg a day, to be increased by 50mg a day qW to 400 mg a day. DVd was repeated q4 W, for a minimum of 6 cycles 2 cycles after best response. Pts were maintained on prednisone 50 mg qod the MTD of T until disease progression. 50 pts were enrolled in each group. 45 pts in the Nmm and Rmm had sufficient follow up to be reported. Rmm pts were older (median 64 vs. 58 years), tended to have a worse performance status (P.S. 0) (22% vs. 42%), and a higher baseline b2 microglobulin level (mean 6.6 vs. 4.6 mg/L) as compared to the Nmm. Overall, both groups received a median of 6 cycles of therapy. Following an increased incidence of neutropenia, infections, paraesthesia and DVT in the first 11 Nmm and 20 Rmm pts; the protocol was amended to initiate pts on prophylactic amoxicillin 250mg BID, acyclovir 400 mg BID ASA 81 mg/d. GM-CSF or G-CSF was given if the total WBC was less than 5000/ L on day 1 of therapy and a more aggressive V dose reduction schema was adopted. Following these amendments the incidence of pneumonia dropped from 8 cases in the Rmm to none in the next 25 enrolled patients, and no neutropenia requiring therapy reported in any of the groups. DVT was reduced from an overall rate of 33% to 10%. The overall CR/ NCR rates were virtually identical for both Nmm (46%) and Rmm pts (47%), as was the time to best response (median of 4.2 months for both groups). Stable disease or better occurred in 84% and 89% of the Nmm and Rmm respectively. DVd in combination with T and the appropriate supportive care measures resulted in a high response rate as well as an improved quality of response similar to what is achieved with high dose therapy. This regimen was well tolerated and the bone marrow reserves did not seem to be compromised. A randomized study comparing DVd-T to bone marrow transplantation should be considered.
|
Cleveland Clinic Home |
Contact Us |
Disclaimer |
Privacy Statement
Page Last Updated 04/12/2004 11:02:57 PM |
Questions,
Suggestions or to Enquire about a trial
Maps & Directions