Clinical Efficacy of Pegylated Liposomal Doxorubicin, Vincristine and Dexamethasone in Patients with Newly Diagnosed Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5212-5212
Author(s):  
Wen Wu ◽  
Xiaodong Gao ◽  
Lan Xu ◽  
Hua Yan ◽  
Zhixiang Shen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Partial Response ◽  
Adverse Events ◽  
Median Time ◽  
Liposomal Doxorubicin ◽  
Gastrointestinal Symptoms ◽  
Pegylated Liposomal Doxorubicin ◽  
High Response Rate ◽  
Newly Diagnosed

Abstract Object: To investigate the short-term and long-term efficacy and toxicity of pegylated liposomal doxorubicin, vincristine and dexamethasone (DVD) in patients with newly diagnosed multiple myeloma (MM). Methods: Twenty-five patients (13 males, 12 females, median age 55 years) with newly diagnosed multiple myeloma were treated with pegylated liposomal doxorubicin 40 mg/m2 and vincristine 2 mg intravenously on day 1 plus dexamethasone 40 mg intravenously or orally on days 1–4 (DVD) for median 4.5 (2–8) cycles. Treatment was repeated every 4 weeks. Response was evaluated according to the International Uniform Response Criteria for Multiple Myeloma (2006) before initiation of each course. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria, version 3.0. Results: After 4.5 (2–8) courses of the median cycles, clinical response was observed in 20 patients (80%), including complete response in 4 (16%), very good partial response in 3 (12%), partial response in 10 (40%), minimal response in 3 (12%) and stable disease in 2 (8%). The median time to initial response was 1.2 months and the median time to best response was 4 months. After 25 (2–50) months of median follow-up, the median progression-free survival was 20 months, while the median overall survival has not yet been reached. The overall survival rate was 72% (18/25). The most common adverse events were gastrointestinal symptoms (nausea and vomiting in 10, constipation in 9 patients), neutropenia (7 patients), anemia (6 patients) and thrombocytopenia (4 patients). DVD was associated with more hand-foot syndrome (4 patients) and mucitis (2 patients). Conclusions: DVD scheme is an effective therapy with a high response rate and manageable toxicities for patients with newly diagnosed multiple myeloma.

scholarly journals Lenalidomide, bortezomib, pegylated liposomal doxorubicin, and dexamethasone in newly diagnosed multiple myeloma: a phase 1/2 Multiple Myeloma Research Consortium trial

Blood ◽  
2011 ◽  
Vol 118 (3) ◽  
pp. 535-543 ◽  
Author(s):  
Andrzej J. Jakubowiak ◽  
Kent A. Griffith ◽  
Donna E. Reece ◽  
Craig C. Hofmeister ◽  
Sagar Lonial ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Liposomal Doxorubicin ◽  
Phase 1 ◽  
Pegylated Liposomal Doxorubicin ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Newly Diagnosed

Abstract This phase 1/2 trial evaluated combination lenalidomide, bortezomib, pegylated liposomal doxorubicin, and dexamethasone (RVDD) in newly diagnosed multiple myeloma (MM) patients. Patients received RVDD at 4 dose levels, including the maximum tolerated dose (MTD). Patients with a very good partial response or better (≥ VGPR) after cycle 4 proceeded to autologous stem cell transplantation or continued treatment. The primary objectives were MTD evaluation and response to RVDD after 4 and 8 cycles. Seventy-two patients received a median of 4.5 cycles. The MTDs were lenalidomide 25 mg, bortezomib 1.3 mg/m2, pegylated liposomal doxorubicin 30 mg/m2, and dexamethasone 20/10 mg, as established with 3-week cycles. The most common adverse events were fatigue, constipation, sensory neuropathy, and infection; there was no treatment-related mortality. Response rates after 4 and 8 cycles were 96% and 95% partial response or better, 57% and 65% ≥ VGPR, and 29% and 35% complete or near-complete response, respectively. After a median follow-up of 15.5 months, median progression-free survival (PFS) and overall survival (OS) were not reached. The estimated 18-month PFS and OS were 80.8% and 98.6%, respectively. RVDD was generally well tolerated and highly active, warranting further study in newly diagnosed MM patients. This trial was registered at www.clinicaltrials.gov as NCT00724568.

scholarly journals Subcutaneous Administration of Bortezomib in Combination with Thalidomide and Dexamethasone for Treatment of Newly Diagnosed Multiple Myeloma Patients

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Shenghao Wu ◽  
Cuiping Zheng ◽  
Songyan Chen ◽  
Xiaoping Cai ◽  
Yuejian Shi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Adverse Events ◽  
Subcutaneous Administration ◽  
Progression Free Survival ◽  
The Other ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Grade 3

Objective. To investigate the efficacy and safety of the treatment of the newly diagnosed multiple myeloma (MM) patients with the therapy of subcutaneous (subQ) administration of bortezomib and dexamethasone plus thalidomide (VTD) regimen.Methods. A total of 60 newly diagnosed MM patients were analyzed. 30 patients received improved VTD regimen (improved VTD group) with the subQ injection of bortezomib and the other 30 patients received conventional VTD regimen (VTD group).The efficacy and safety of two groups were analyzed retrospectively.Results. The overall remission (OR) after eight cycles of treatment was 73.3% in the VTD group and 76.7% in the improved VTD group (P>0.05). No significant differences in time to 1-year estimate of overall survival (72% versus 75%,P=0.848) and progression-free survival (median 22 months versus 25 months;P=0.725) between two groups. The main toxicities related to therapy were leukopenia, neutropenia, thrombocytopenia, asthenia, fatigue, and renal and urinary disorders. Grade 3 and higher adverse events were significantly less common in the improved VTD group (50%) than VTD group (80%,P=0.015).Conclusions. The improved VTD regimen by changing bortezomib from intravenous administration to subcutaneous injection has noninferior efficacy to standard VTD regimen, with an improved safety profile and reduced adverse events.

An Open-Label Study of Pegylated Liposomal Doxorubicin, Vincristine and Reduced-Dose Dexamethasone Combination Therapy in Newly Diagnosed Multiple Myeloma Patients in Chinese Population.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4816-4816
Author(s):  
Yang Shen ◽  
Zhixiang Shen ◽  
Bin Jiang ◽  
Jian Hou ◽  
Rong Zhan ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Chinese Population ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Combination Regimen ◽  
Newly Diagnosed ◽  
Open Label ◽  
Open Label Study ◽  
Reduced Dose

Abstract BACKGROUND: Pegylated liposomal doxorubicin (CAELYX®) is a liposomal formulation of doxorubicin sterically stabilized by the grafting of segments of polyethylene glycol (PEG) onto the liposomal surface. Given the demonstrated efficacy of VAD (vincristine and doxorubicin and oral dexamethasone) in Multiple Myeloma (MM) patients and the potential for CAELYX® to extend the duration of bone marrow exposure to therapeutic levels of doxorubicin, a combination regimen of CAELYX®, vincristine, and reduced-dose dexamethasone (DVD) has been actively investigated in MM patients. Studies showed that substituting CAELYX® for doxorubicin in the VAD regimen and reducing the dose of dexamethasone in MM patients improves the safety profile and convenience of the treatment regimen without compromising efficacy. Due to potential differences in metabolism of these patients, safety and efficacy results may vary. Thus, we carried out this study in 82 newly diagnosed MM patients in China, in order to demonstrate the efficacy and safety profiles of DVD. METHODS: Patients (n=82) from 15 sites were recruited in this study. CAELYX® (40mg/m2) was infused intravenously over 60-minutes, administered every 28 days. Vincristine (2.0mg) was administered intravenously on Day 1 of each cycle. Dexamethasone (40 mg) was administered from Day 1- Day 4 of each cycle orally or intravenously. The treatment was repeated every 28 days for 4 cycles. RESULTS: Upon ITT analysis, the overall response rate was approximately 68% (56/82); 11% of the patients achieved complete remission (CR), 40% achieved partial response (PR), 17% achieved minimal response; 15% had stable disease (SD), and 12% o had progressive disease (PD) after the treatment. The cumulative 4-month progression-free survival (PFS) was 88%. The incidence of all the adverse events was 46%. The most common non-hematological toxicities were palmar-plantar erythrodysesthesia (13.4%) and stomatitis (6.1%), respectively. CONCLUSION: Pegylated liposomal doxorubicin, vincristine and reduced dose dexamethasone combination (DVD) regimen is an effective and safe regimen in newly diagnosed multiple myeloma patients in Chinese population.

A Phase II Study of Pegylated Liposomal Doxorubicin, Bortezomib and Dexamethasone (DVD) for Patients with Previously Untreated Multiple Myeloma (MM).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4936-4936
Author(s):  
James R. Berenson ◽  
Ori Yellin ◽  
Ravi Patel ◽  
Chien-Shing Chen ◽  
Ralph Vincent Boccia ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Peripheral Neuropathy ◽  
Adverse Events ◽  
Phase Ii ◽  
Liposomal Doxorubicin ◽  
Phase Ii Study ◽  
Severe Combined Immunodeficiency ◽  
Pegylated Liposomal Doxorubicin ◽  
Pulmonary Interstitial Fibrosis ◽  
Grade 3

Abstract Abstract 4936 Despite recent advances in the treatment of MM, the disease remains incurable and many of the most effective, newer combination therapies are accompanied by significant side effects that have a major negative impact on the patient's quality of life. Pegylated liposomal doxorubicin (PLD) and bortezomib have shown anti-MM efficacy in the laboratory and for the treatment of previously treated MM patients, leading to FDA approval for patients who have failed one prior therapy. Using our severe combined immunodeficiency-hu murine models of human MM, we have previously demonstrated that lower doses of PLD administered daily are more effective and better tolerated than higher amounts given weekly. Moreover, the combination of bortezomib and dexamethasone has been shown to be effective for previously untreated MM patients. Prior studies by our group have shown that combining chemotherapy including PLD with bortezomib administered at 1.0 mg/m2 on days 1, 4, 8, and 11 of a 28-day cycle rather than the standard 1.3 mg/m2 on the same days of a 21-day schedule is effective for MM patients with relapsed or refractory disease and associated with a reduction in the incidence and severity of peripheral neuropathy. Thus, we conducted a single-arm multi-center phase II study for previously untreated MM patients to evaluate the combination of intravenously administered dexamethasone, bortezomib and PLD (DVD). The treatment consisted of intravenous administration of 40 mg dexamethasone followed by 1.0 mg/m2 bortezomib and finally 5.0 mg/m2 PLD on days 1, 4, 8, and 11 of a 28-day cycle. Patients were treated to a maximum response plus two additional cycles or completed a maximum of eight cycles of therapy without disease progression. To date, 22 (of 35 planned) patients have been enrolled with a median age of 64 years (range, 42-79 years). The majority of those on study (68 %) were diagnosed with International Staging System II or III MM. Four patients are too early to assess for response. To date, among the 18 evaluable patients, 16 (89%) have shown objective responses to the DVD regimen, including 2 complete responses (11%), 8 partial responses (44%) and 6 minimal responses (33%). The other 2 patients (11%) had stable disease, with one of these subjects showing a continuing reduction in M-protein after 2 cycles of therapy to date. Thus, disease control was achieved in all patients. To date, no patient has shown progressive disease after 2+ - 12+ months of follow-up. Six patients experienced grade 3 adverse events and one patient with a prior history of pulmonary interstitial fibrosis developed a grade 4 toxicity (shortness of breath). Grade 3 adverse events in three of the six patients were judged not to be related to the study treatment. The most common grade 3 adverse event was reversible neutropenia (n=2). To date, only 2 patients (9%) have developed peripheral neuropathy (grade 1). Notably, there have been no cases of stomatitis or hand-foot syndrome. Thus, these results suggest that the DVD regimen using a modified schedule and doses of the combination of intravenous dexamethasone, bortezomib and PLD is a well tolerated treatment that produces high response rates for previously untreated patients with multiple myeloma. Disclosures Berenson: Millennium Pharmaceuticals: Consultancy, Research Funding, Speakers Bureau; Centocor Ortho Biotech: Consultancy, Speakers Bureau. Hilger:Millennium Pharmaceutcals: Employment.

Combination therapy based on bortezomib for 102 patients with newly-diagnosed multiple myeloma: a Chinese experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5116-5116
Author(s):  
Jingsong He ◽  
Li Yang ◽  
Xiaoyan Han ◽  
Gaofeng Zheng ◽  
Xiaojian Meng ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Peripheral Neuropathy ◽  
Combination Therapy ◽  
Adverse Events ◽  
Chinese Population ◽  
Median Overall Survival ◽  
Chinese Patients ◽  
Newly Diagnosed ◽  
Significant Difference

Abstract Abstract 5116 Multiple myeloma (MM) is a malignant neoplasm of plasma. The rates of complete remission (CR) or very good partial remission (VGPR) for patients received conventional chemotherapy are still low with median overall survival about 3 years. Here we report our results with combination therapy based on bortezomib in the Chinese population and investigat the efficacy and safety of Bortezomib-based therapies in previously untreated MM patients. Metohds: Between 1st Feb. 2006 and 31st Dec. 2010, 102 consecutive newly-diagnosed patients with symptomatic MM were treated with combination therapies based on bortezomib. Sixty-four patients were male and 38 were female. Median age was 59 years (range 31–86 years). Forty-two patients were stage 3 according to the International Staging System, 36 patients were stage 2 and 24 patients were stage 1. The combinations included dexamethasone (BD group ), dexamethasone plus subsequent thalidomide (BDT group ) and dexamethasone plus cyclophosphamide (BDC group ) or epirubicin (BDA group ) based on bortezomib. Thirty-five patients were in BDT group, 19 in BD group, 32 in BDC group and 16 in BDA. All patients received a median of three cycles of therapy (range 1–5 ). The IMWG criteria was used for response evaluation and toxicities were evluated according to the NCI Common Toxicity Criteria version 3. Results: The efficacy of the triplet combination therapy based on bortezomib including BDT, BCD and BAD were better than BD group, with response rate greater than or equal to partial remission(≥PR) 85.7%, 90.6%, 93.7% and 68.4%, respectively. The efficacy of BDA and BDC group were significantly superior to BD group (P=0.048,0.050). Bortezomib in combination with chemotherapy was highly effective as treatment for symptomatic multiple myeloma, even only after one cycle. The efficacy for patients received one cycle of BDT, BD, BCD and BAD was 65.7%, 42.1%, 65.6% and 62.5%, respectively. Patients treated with BD had suboptimal responses to those received BDT, BCD and BAD treatment and one cycle of BCD was superior to one cycle of BD (P=0.019).The median follow-up time was 17m (1–60m), including 31m (1–60m) for 35 patients in BDT group and 16m (2–29m) for the remaining 67 patients. The median progression-free survival (PFS ) of BDT group was 15m (9.8–20.2m ) while BD group was 12m (8.1–15.8m), BCD group was 13m (5.9–20.1m ), and BAD group was 12m (7.8–16.2m ), without significant difference. The median overall survival (OS ) of BDT group was 35m (13.2–56.8m ) while BD, BCD and BAD groups was not reached yet. There was no significant difference in OS among groups, but BCD and BAD were superior to BD group (P=0.104, 0.142 ). The frequent treatment-emergent adverse events includes hematologic adverse events such as neutropenia, anemia, thrombocytopenia and the non-hematologic adverse events like fatigue, infection, constipation, diarrhea, pleural effusion and ascites, herpes zoster and peripheral neuropathy. Patients treated with BDT were more likely to show peripheral neuropathy than those treated with BD, BCD and BAD (91.4% vs 73.6%, 68.7%, 74.9% ), but there is no statistical significant difference (P = 0.131), Grade 2 or 3 peripheral neuropathy was occurred in 45.7% of BDT group significantly higher than BD, BCD and BAD groups. (21.0%, 15.7% and 18.7%, P = 0.028 ). Other related adverse events in all the groups had no significant difference. Routine anticoagulation or anti-thrombsis were not used. Only 1 patient suffered from DVT/PE but did well with treatment. Conclusions: Our preliminary experience in Chinese patients indicated that combination chemotherapy based on bortezomib is highly effective in newly-diagnosed multiple myeloma and BDC, BDA or BDT regimens may be more superior to BD in Chinese population. There were relative lower rates of DVT/PE in the Chinese patients with MM received combination chemotherapy based on bortezomib. Disclosures: No relevant conflicts of interest to declare.

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