Pegylated liposomal doxorubicin, vincristine, and reduced-dose dexamethasone as first-line therapy for multiple myeloma

In patients with multiple myeloma (MM) who may ultimately receive active therapy, the combination of VAD (vincristine, doxorubicin, and dexamethasone) has been shown to be effective. However, the use of VAD is complicated by inherent risks that result from the use of central venous catheters, steroid toxicity, and by doxorubicin-associated adverse events such as cardiotoxicity and alopecia. To address these issues, a phase II trial investigating the combination of vincristine, pegylated liposomal doxorubicin, and reduced-schedule oral dexamethasone in the first-line treatment of patients with MM has been conducted. Patients with symptomatic, newly diagnosed MM were treated with intravenous (i.v.) pegylated liposomal doxorubicin 40 mg/m2 and vincristine 2 mg on day 1, along with dexamethasone 40 mg/day given either i.v. or orally for 4 days, every 4 weeks for a minimum of 6 cycles. Responses were reported in 29 patients (88%), and an additional 3 patients achieved stable disease. The median time to maximal response was 5.8 months (range, 0.7-13.6 months), and median overall survival time is estimated to be 60 months. This treatment regimen was well tolerated, and the most common grade 3/4 adverse events included hand-foot syndrome (21%), neutropenia (30%), anemia (21%), and mucositis (12%). Based on these results, the vincristine/liposomal doxorubicin/dexamethasone regimen appears to be effective and well tolerated in the first-line treatment of MM.     

Primary treatment of multiple myeloma with thalidomide, vincristine, liposomal doxorubicin and dexamethasone (T-VAD doxil): a phase II multicenter study.

BACKGROUND: High-dose chemotherapy with autologous stem cell transplantation after initial cytoreductive chemotherapy with the combination vincristine, doxorubicin and dexamethasone (VAD) is considered an effective therapy for many patients with newly diagnosed, symptomatic multiple myeloma. Response to initial cytoreductive chemotherapy is important for the long-term outcome of such patients. Thalidomide has recently shown significant antimyeloma activity. We studied the efficacy and toxicity of the combination of a liposomal doxorubicin-containing VAD regimen with thalidomide, administered on an outpatient basis, as initial cytoreductive treatment in previously untreated patients with symptomatic myeloma. PATIENTS AND METHODS: Thirty-nine myeloma patients were treated with vincristine 2 mg intravenously (i.v.), liposomal doxorubicin 40 mg/m(2) i.v. administered as single dose on day 1, and dexamethasone 40 mg per os daily for 4 days. Dexamethasone was also given on days 15-18 of the first cycle of treatment. The regimen was administered every 4 weeks for four courses. Thalidomide was given daily at a dose of 200 mg at bedtime. Response to treatment was evaluated after four cycles of treatment. After completion of four cycles, the patients were allowed to proceed to high-dose chemotherapy or to receive two additional cycles of the same treatment. RESULTS: On an intention-to-treat basis, 29 of the 39 patients (74%) responded to treatment. Four patients (10%) achieved complete and 25 (64%) partial response. Three patients (8%) showed minor response and seven (18%) were rated as non-responders. Major grade 3 or 4 toxicities consisted of neutropenia (15%), thrombocytopenia (15%), deep vein thrombosis (10%), constipation (10%), skin rash (5%) and peripheral neuropathy (5%). Two patients (5%) experienced early death due to infection. CONCLUSIONS: The combination of vincristine, liposomal doxorubicin, and dexamethasone (VAD doxil) with thalidomide is an effective and relatively well-tolerated initial cytoreductive treatment.Prospective randomized studies are required in order to assess the effect of this regimen on the long-term outcome of patients with multiple myeloma.     

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

OBJECTIVE Though doxorubicin is highly active in the treatment of multiple myeloma, its toxicity profile limits its therapeutic index. We performed this study to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD, CaelyxR), vincristine, and reduced-dose dexamethasone combination therapy in newly diagnosed multiple myeloma (MM) patients in a Chinese population. METHODS This was an open-label, single-arm study in which newly diagnosed patients with MM received PLD 40 mg/m2 intravenously on Day 1, vincristine 1.4 mg/m2 intravenously (maximum 2 mg) on Day 1, and 40 mg of dexamethasone (intravenously or orally) from Day 1 to Day 4. Treatment was repeated every 28 days for at least 4 cycles. RESULTS In the intent-to-treat (ITT) analysis, the overall response rate was 68.29%, and the complete remission rate was 10.98%. The incidence of all adverse events was 46.34%. The most common non-hematologic toxicities were palmar-plantar erythrodysesthesia (13.4%) and stomatitis (6.1%). CONCLUSION PLD, vincristine, and a reduced-dose dexamethasone combination (DVd) is an effective and safe regimen in newly diagnosed MM patients in a Chinese population.     

Phase II study of CLAD (cyclophosphamide, liposomal doxorubicin and dexamethasone) in patients with advanced multiple myeloma and historical comparison to CAD (cyclophosphamide, doxorubicin and dexamethasone)

The purpose of this study was to assess the efficacy and safety of pegylated liposomal doxorubicin in combination with cyclophosphamide and dexamethasone (CLAD). In this prospective open-label phase II study, 60 patients with advanced multiple myeloma (MM) received three weekly cycles of CLAD, consisting of cyclophosphamide 200 mg/m2 i.v. d1-4, pegylated liposomal doxorubicin 20 mg/m2 i.v. d1 and dexamethasone 40 mg p.o. d1-4 for a maximum of six cycles in absence of disease progression. Efficacy and toxicity was compared to our immediate historical cohort of 46 patients treated with cyclophosphamide, dexamethasone and conventional doxorubicin (CAD). A total of 239 cycles of CLAD and 209 cycles of CAD, respectively, were given. The objective response rate was 71% (CLAD) and 74% (CAD). Non-cumulative hematological toxicity was predominant in both regimens. It was found that CLAD is an active and well-tolerated treatment regimen for MM. Response rate is comparable to other anthracycline containing regimens like CAD with an advantage in hematological toxicity and lower infectious complications, and a presumed advantage of lower cardiotoxicity.     

Pegylated liposomal doxorubicin, vincristine, and dexamethasone provide significant reduction in toxicity compared with doxorubicin, vincristine, and dexamethasone in patients with newly diagnosed multiple myeloma: a Phase III multicenter randomized trial

BACKGROUND: Pegylated liposomal doxorubicin has pharmacologic and safety advantages over conventional doxorubicin. METHODS: For this noninferiority trial, 192 patients with newly diagnosed, active multiple myeloma were randomized to receive either combined pegylated liposomal doxorubicin (40 mg/m(2)) and vincristine (1.4 mg/m(2); maximum, 2.0 mg) as an intravenous infusion on Day 1 plus reduced-dose dexamethasone (40 mg) orally on Days 1-4 (DVd) (n = 97 patients) or combined vincristine (0.4 mg per day) and conventional doxorubicin (9 mg/m(2) per day) as a continuous intravenous infusion on Days 1-4 plus reduced-dose dexamethasone (VAd) (n = 95 patients) for at least 4 cycles. Treatment was repeated every 4 weeks until patients either achieved maximal response, disease progression, or unacceptable toxicity or underwent transplantation. The primary endpoints were response and toxicity. RESULTS: Objective response rates (DVd, 44%; VAd, 41%), progression-free survival (hazard ratio, 1.11; P = 0.69), and overall survival (hazard ratio, 0.88; P = 0.67) were similar between the treatment groups. However, DVd was associated with significantly less Grade 3/4 neutropenia or neutropenic fever (10% vs. 24%; P = 0.01), a lower incidence of sepsis, and less antibiotic use. Compared with VAd, DVd also significantly decreased the need for central venous access (P < 0.0001) and growth-factor support (P = 0.03) and resulted in less alopecia (20% vs. 44%; P < 0.001) but more hand-foot syndrome (25% vs. 1%; P < 0.001), mainly Grade 1/2. CONCLUSIONS: The DVd regimen demonstrated similar efficacy with less toxicity and supportive care compared with VAd, which should improve clinical utility and optimize the opportunity for transplantation.     

Combination regimens using doxorubicin and pegylated liposomal doxorubicin prior to autologous transplantation in multiple myeloma

Doxorubicin and pegylated liposomal doxorubicin are key compounds of several induction regimens used prior to autologous stem cell transplantation in patients with de novo multiple myeloma, such as vincristine, doxorubicin, dexamethasone (VAD), vincristine, pegylated liposomal doxorubicin/Doxil^®, dexamethasone (DVd) or PS-341/bortezomib, doxorubicin, dexamethasone (PAD). The aim of this article is to summarize the more recent data available on the efficacy of these combinations and to discuss their role as part of initial therapy.     

Clinical benefits and economic analysis of pegylated liposomal doxorubicin/vincristine/dexamethasone versus doxorubicin/vincristine/dexamethasone in patients with newly diagnosed multiple myeloma

Pegylated liposomal doxorubicin has reduced toxicity compared with conventional doxorubicin. In a noninferiority trial randomizing patients to receive pegylated liposomal doxorubicin 40 mg/m(2) and vincristine 1.4 mg/m(2) (maximum, 2 mg) intravenously on day 1 plus reduced-dose dexamethasone 40 mg orally on days 1-4 (DVd; n = 97) or conventional doxorubicin 9 mg/m(2) per day and vincristine 0.4 mg per day continuous intravenous infusion on days 1-4 plus reduced-dose dexamethasone (VAd; n = 95) for >/= 4 cycles. Treatment was repeated every 4 weeks until maximal response, disease progression, unacceptable toxicity, or until patients underwent transplantation. Treatment cost was estimated by applying standard US costs in 2004 to recorded health-care resource utilization units. Outcome measures included response, toxicity, and treatment cost. Objective response rates (DVd, 44%; VAd, 41%), progression-free survival (hazard ratio, 1.11; P = 0.69), and overall survival (hazard ratio, 0.88; P = 0.67) were similar between treatment groups. DVd was associated with significantly less grade 3/4 neutropenia or neutropenic fever (10% vs. 24%; P = 0.01), less sepsis, antibiotic use, growth factor support, and alopecia, but more hand-foot syndrome. Study drug costs were significantly higher for DVd versus VAd; however, lower costs for drug administration and supportive care more than offset this difference, resulting in nominally lower overall study drug treatment costs for DVd (DVd, $34,442; VAd, $35,846; P = 0.76). The DVd regimen demonstrated similar efficacy and cost with less toxicity and supportive care compared with VAd. This should improve clinical utility and optimize the opportunity for transplantation.     

Liposomal daunorubicin (DaunoXome) plus dexamethasone for patients with multiple myeloma. A phase II International Oncology Study Group study

BACKGROUND: Liposomal daunorubicin is an effective cytotoxic agent in patients with Kaposi sarcoma and hematologic malignancies. Anthracycline-based chemotherapy regimens, such as vincristine/doxorubicin/dexamethasone (VAD), are standard in the treatment of patients with multiple myeloma (MM). Cardiotoxicity remains a limiting factor in dose escalation of anthracyclines, and multidrug resistance (MDR) develops rapidly on exposure to anthracyclines. Liposomal daunorubicin was designed in an attempt to overcome MDR and to reduce anthracycline-related toxicities. Thus, an open-label, Phase II clinical study was conducted by the International Oncology Study Group to assess the efficacy and safety of intravenous liposomal daunorubicin at a dose of 100 mg/m2 given every 3 weeks for a maximum of 6 cycles in patients with recently diagnosed MM (n = 4 patients) or recurrent/refractory MM (n = 37 patients). METHODS: Liposomal daunorubicin was administered as a single agent for the initial two cycles of therapy, and dexamethasone was added to all subsequent cycles. The primary study end point was response rates. Thirty-eight patients were treated, 35 of whom were evaluable for response. RESULTS: A partial response was achieved in six patients (17%), including one patient with disease that previously was refractory to VAD therapy. Stable disease was observed in 22 patients (63%). The principal toxicity was myelosuppression. Grade 3 or 4 hematologic toxicities included granulocytopenia (26%), anemia (Grade 3 only; 11%), thrombocytopenia (11%), and febrile neutropenia (13%). The median survival in 35 patients with recurrent disease was 7.6 months. CONCLUSIONS: Liposomal daunorubicin had activity in this population of poor-risk patients that was comparable to the activity of standard regimens. Further studies of this agent in combination with other anti-MM agents are warranted.     

Prospective randomized comparison of vincristine, doxorubicin and dexamethasone (VAD) administered as intravenous bolus injection and VAD with liposomal doxorubicin as first-line treatment in multiple myeloma.

BACKGROUND: The combination of vincristine and doxorubicin administered as a continuous infusion via an indwelling catheter together with intermittent high-dose dexamethasone (VAD) is an effective primary treatment for patients with symptomatic multiple myeloma. In order to avoid the need for an indwelling catheter, which imposes logistic problems for outpatient administration, several phase II studies have explored the feasibility and efficacy of VAD-like outpatient regimens. We designed a prospective randomized study to compare the objective response rates of two VAD-like outpatient regimens as primary treatment for symptomatic patients with multiple myeloma. PATIENTS AND METHODS: Patients were entered in a randomized study regardless of age, performance status and renal function. One hundred and twenty-seven patients received VAD bolus, which consisted of vincristine 0.4 mg i.v., doxorubicin 9 mg/m(2) i.v. and dexamethasone 40 mg p.o. daily for four consecutive days and 132 patients received VAD doxil, which consisted of vincristine 2 mg i.v. and liposomal doxorubicin 40 mg/m(2) i.v. on day 1 and dexamethasone 40 mg p.o. daily for 4 days. The two regimens were administered every 28 days for four courses and in courses 1 and 3, in both arms, dexamethasone was also given on days 9-12 and 17-20. RESULTS: An objective response was documented in 61.4% and 61.3% of patients treated with VAD bolus and VAD doxil, respectively. Hematological and non-hematological toxicities were mild or moderate and equally distributed between the two treatment arms with the exception of alopecia, which was more common after VAD bolus, and of palmar-plantar erythrodysesthesia, which was more common after VAD doxil. CONCLUSIONS: Our multicenter trial, which included an unselected patient population, indicated that both VAD bolus and VAD doxil can be administered to outpatients and can provide an equal opportunity of rapid response in many patients with multiple myeloma.     

硼替佐米联合阿霉素、地塞米松治疗初治多发性骨髓瘤的疗效观察

目的　比较硼替佐米联合阿霉素、地塞米松方案（ＰＡＤ方案）与长春新碱联合阿霉素、地塞米松方案（ＶＡＤ方案）治疗初治多发性骨髓瘤（ＭＭ）的疗效和不良反应。方法　ＰＡＤ方案组４１例患者给予硼替佐米１.３ｍｇ／ｍ２静推,第１、４、８、１１天;阿霉素１０ｍｇ／ｄ静滴,第１～４天;地塞米松２０ｍｇ／ｄ静滴,第１～４天,３周为１个周期,每例接受２～６个周期化疗。４０例ＶＡＤ方案组患者予长春新碱０.５ｍｇ／ｄ静滴,第１～４天;阿霉素１０ｍｇ／ｄ静滴,第１～４天;地塞米松２０ｍｇ／ｄ静滴,第１～４天,４周为１个周期,每例接受２～８个周期化疗。化疗２个周期后评价两组患者的疗效和不良反应。结果　两组患者均可评价疗效和不良反应。化疗２个周期后,ＰＡＤ方案组获显效２２例（５３.７％）,ＶＡＤ方案组获显效１０例（２５.０％）,差异有统计学意义（Ｐ＜０.００１）。两组主要不良反应包括消化道症状、周围神经炎、血小板减少、白细胞减少和感染,多为１～２级,经对症治疗后均可缓解。结论 ＰＡＤ方案治疗初治ＭＭ的显效率明显高于ＶＡＤ方案,不良反应可耐受。     

小剂量沙利度胺联合含单周地塞米松的VAD方案治疗多发性骨髓瘤42例

目的观察小剂量沙利度胺联合含单周地塞米松的VAD方案治疗多发性骨髓瘤（MM）的临床疗效及不良反应。方法给予42例MM患者小剂量沙利度胺（150～200）mg／d联合含单周地塞米松（40mg,口服,第1天至第4天）的VAD方案治疗,28d为1个疗程。4个疗程后进行总体评估。结果总有效率为80．95％（34／42）;其中完全缓解6例,部分缓解20例,进步8例,无效8例。不良反应轻微,患者治疗前后血红蛋白、骨髓浆细胞比例、β2微球蛋白、Karnofsky评分、血肌酐、血免疫球蛋白差异均有统计学意义（均P〈0．001）。结论小剂量沙利度胺联合含单周地塞米松的VAD方案治疗MM有效率高,不良反应轻微,值得临床进一步研究和推广应用。     

Phase I study of weekly paclitaxel and liposomal doxorubicin in patients with advanced solid tumours

The aim of this study was to determine the maximum tolerated dose (MTD) and the dose-limiting toxicities (DLT) of a weekly administration of paclitaxel and pegylated liposomal doxorubicin (Caelyx; Schering Plough Pharmaceutical) in patients with advanced solid tumours. 19 pretreated patients with solid tumours received escalated doses of pegylated liposomal doxorubicin (6-12 mg/m(2)) as a 1-h intravenous (i.v.) infusion followed by a fixed dose of paclitaxel (80 mg/m(2)) weekly for 4 consecutive weeks in cycles of 6 weeks. DLT was defined as grade 4 neutropenia or thrombocytopenia, febrile neutropenia, grades 3 or 4 non-haematological toxicity or treatment delay due to unresolved toxicity during cycle 1. The MTD was reached at the dose of pegylated liposomal doxorubicin of 10 mg/m(2)/week and paclitaxel of 80 mg/m(2)/week. The DLTs were treatment delay due to grade 3 neutropenia and grade 3 diarrhoea. A total of 55 chemotherapy cycles were administered, and grades 3-4 neutropenia occurred in seven cycles (13%); the non-haematological toxicity was mild with grades 2/3 diarrhoea occurring in 4 (7%), grades 2-4 asthenia in 11 (20%) and grade 2 mucositis in 7 (13%) cycles. There was no case with more than a 10% LVEF decrease after a median of 3 (range 2-6) administered cycles/patients. One patient with breast cancer and 1 with ovarian cancer experienced a major partial response. The weekly administration of pegylated liposomal doxorubicin at the dose of 10 mg/m(2) in combination with paclitaxel at the dose of 80 mg/m(2) for 4 consecutive weeks, in cycles of 6 weeks which represent the recommended doses for further phase II studies, is a well tolerated regimen, which merits further evaluation in tumours known to be sensitive to taxanes and/or anthracyclines.     

Weekly Bortezomib,Pegylated Liposomal Doxorubicin,and Dexamethasone Is a Safe and Effective Therapy for Elderly Patients With Relapsed/Refractory Multiple Myeloma

BackgroundThe synergic, additive effect of bortezomib and pegylated liposomal doxorubicin (PLD) has never been tested in an elderly group of patients with relapsed/refractory multiple myeloma (MM).Patients and Methods:In this study, 25 patients with a median age of 75 years were treated with bortezomib at usual doses of 1.3 mg/m² every 21 days. After 2 cycles, bortezomib was given intravenously (I.V.) weekly every 32 days. Pegylated liposomal doxorubicin 30 mg/m² I.V. was given on day 4 for 2 cycles and then was given on day 8. Dexamethasone 40 mg I.V. was given on days 1-4 for 2 cycles and then 20 mg weekly.Results:Bortezomib/PLD/dexamethasone therapy resulted in 20 of 25 objective responses for an overall response rate of 80% (complete remission + very good partial remission, 66%). Median overall survival was not reached. Median duration of response (progression-free survival) was 8 months. Eleven of 16 patients (68%) with ≥ VGPR still maintain a response at a median of 12 months versus 4 months for patients with < VGPR (PFS, overall survival; P = .0001). Grade 3/4 toxicities were mild in most of the patients.ConclusionBortezomib/PLD/dexamethasone combination is safe and effective in elderly patients with resistant-relapsing MM.     

VAD方案治疗多发性骨髓瘤疗效观察

 目的 评估VAD方案治疗多发性骨髓瘤（MM）的疗效。方法 24例Ⅲ期MM,采用VAD方案,即长春新碱0.5 mg／d（或长春地辛1 ~ 2 mg／d）缓慢静脉注射,第1～4天;多柔比星（或表柔比星）10 ~ 20 mg／d缓慢静脉注射,第1～4天;地塞米松40 mg／d口服,第1～4天,第9～12天,第17～20天,28 d为1疗程。连续应用2疗程以上评估疗效。观察项目包括：血清M蛋白、肝肾功能、尿蛋白、骨髓穿刺、血象等,记录毒副反应。MM疗效标准,分为完全缓解（CR）、部分缓解（PR）、未缓解（NR）。结果 CR8例（33.3 %）,PR12例（50 %）,NR4例（16.7 %）,总有效率为83.3 %。结论 VAD方案治疗Ⅲ期MM的临床疗效显著,临床症状改善明显。     

Modifications to therapy for multiple myeloma: pegylated liposomal Doxorubicin in combination with vincristine, reduced-dose dexamethasone, and thalidomide

The combination of vincristine, doxorubicin, and dexamethasone is an effective treatment for multiple myeloma that produces a more rapid response than other regimens, probably a function of the high-dose, intense steroid schedule. However, vincristine/doxorubicin/dexamethasone administration requires a 96-hour continuous infusion delivered via a central venous catheter, which necessitates hospitalization in a large number of patients and may increase the risk for infection. Moreover, the high dosages of corticosteroids required with this regimen can cause substantial toxicity. Therefore, a number of modifications to the regimen have been evaluated in an effort to improve its tolerability and efficacy. These include replacing doxorubicin with pegylated liposomal doxorubicin and using a reduced frequency of dexamethasone, and, later, the addition of thalidomide. The results of an ongoing study demonstrated that this latest regimen (including thalidomide) is associated with an improved response rate and a higher quality of response compared with previous regimens in patients with relapsed/refractory multiple myeloma. This modified regimen is well tolerated when prophylactic and supportive measures are incorporated. Although additional follow-up is required to determine the effect on survival, this modified regimen has significant potential in the management of advanced myeloma.     

VAD-doxil versus VAD-doxil plus thalidomide as initial treatment for multiple myeloma: results of a multicenter randomized trial of the Greek Myeloma Study Group.

BACKGROUND: We have previously demonstrated that vincristine, liposomal doxorubicin and dexamethasone (VAD-doxil) is equally effective with VAD-bolus yielding objective response rates of 61% as first-line treatment in multiple myeloma (MM). In a phase II study, the addition of thalidomide to VAD-doxil (TVAD-doxil) proved feasible and increased response rate to 74%. The aim of the present multicenter prospective randomized clinical trial was to compare the efficacy and toxicity of VAD-doxil and TVAD-doxil in previously untreated MM patients. PATIENTS AND METHODS: We enrolled 232 newly diagnosed MM patients aged <75 years, 115 randomized to VAD-doxil (arm A) and 117 to TVAD-doxil (arm B). Patients in arm A received vincristine 2 mg i.v. and liposomal doxorubicin 40 mg/m(2) i.v., on day 1 and dexamethasone 40 mg p.o. daily on days 1-4, 9-12 and 17-20 for the first cycle and on days 1-4 for the next three cycles. Patients in arm B received additionally thalidomide 200 mg p.o. daily, at bedtime. Treatment was administered every 28 days. RESULTS: On an intention-to-treat basis, at least partial response was observed, in 62.6% and in 81.2% of patients randomized to arms A and B, respectively (P = 0.003). Progression-free survival (PFS) at 2 years was 44.8% in arm A and 58.9% in arm B (P = 0.013). Overall survival (OS) at 2 years was 64.6% and 77%, in arms A and B, respectively (P = 0.037). Considering overall toxicity, constipation, peripheral neuropathy, dizziness/somnolence, skin rash and edema were significantly higher in arm B compared with arm A (P < 0.01), but grade 3-4 toxicities were low and similar in both arms. CONCLUSIONS: The addition of thalidomide to VAD-doxil increases response and PFS rates and probably OS in previously untreated myeloma patients. The superiority of efficacy counterbalances the higher overall toxicity of TVAD-doxil.     

硼替佐米联合改良VAD方案治疗多发性骨髓瘤疗效观察

目的:观察硼替佐米联合改良VAD方案（PVAD）治疗多发性骨髓瘤（multiple myeloma）的疗效和安全性。方法:共有52例MM患者接受了2~8个疗程PVAD方案化疗。PVAD方案:硼替佐米（万珂）1.3mg/m2,3秒内快速注射,d1,4,8,11;长春瑞滨10mg/d 静滴,d1~4;吡柔比星10mg/d 静滴,d1~4;地塞米松20mg/d 静滴,d1~4。每28天为1个疗程,观察疗效和不良反应。结果:总体反应率［完全缓解（CR）+接近完全缓解（nCR）+部分缓解（PR）+轻微反应（MR）］为92.3%（48/52）,治疗有效率（CR+PR）为88.5%（46/52）。其中在PVAD方案治疗前接受过VAD方案治疗的21例患者中,18例有效,治疗有效率（CR+PR）为85.7%（18/21）。最常见的血液系统不良反应包括白细胞减少、贫血、血小板减少。非血液系统不良反应主要为乏力、外周神经病变、腹胀/便秘等消化道症状、带状疱疹、呼吸道感染、血栓形成等,经对症处理后均可缓解或恢复。结论:PVAD方案在初发或难治复发的多发性骨髓瘤中均有较好疗效,且具有良好的安全性和耐受性。优于单用硼替佐米或单用VAD方案。     

Pegylated liposomal doxorubicin in the CHOP regimen for older patients with aggressive (stages III/IV) non-Hodgkin's lymphoma

Pegylated liposomal doxorubicin is associated with a lower risk of cardiotoxocity than conventional formulations of doxorubicin, allowing the use of higher cumulative doses. In this Phase II study, 25 patients aged over 70 years (median 79, range 75-82 years) with aggressive non-Hodgkin's lymphoma (NHL) (International Prognostic Index (IPI) -2, 12 (48%); IPI-3, 10 (40%); IPI-4, 3 (12%)) received CHOP with pegylated liposomal doxorubicin. All completed 6 treatment cycles and were evaluable for efficacy and safety. A complete response was achieved in 13 (52%) patients and a partial response in 12 (48%) patients, which was maintained for at least 12 months. The median time to progression was 26 months (range 14->42) and median overall survival was 32 months (range 26-48). No Grades III/IV toxicity occurred; adverse events included neutropenia, anaemia, nausea and vomiting, diarrhoea and constipation in 16-29% of the cycles. Pegylated liposomal doxorubicin is an effective and well-tolerated component that may be substituted for doxorubicin in the CHOPC (cyclophosphanide, doxorubicin, vincristine, prednizolone) regimen for the treatment of aggressive NHL in elderly people.     

Phase II study of pegylated liposomal doxorubicin HCl (Caelyx) in combination with cyclophosphamide and vincristine as second-line treatment of patients with small cell lung cancer

BACKGROUND: Despite chemotherapy and radiotherapy for small cell lung cancer (SCLC), most patients die within 2 years. Response rates for second-line chemotherapy are 15-25%, with a median survival of 5 months. Caelyx, a pegylated liposomal formulation of doxorubicin, may be better tolerated and has activity in SCLC. PATIENTS AND METHODS: Thirty-two patients were enrolled in a phase II study of intravenous Caelyx (35 mg/m2), cyclophosphamide (750 mg/m2) and vincristine (1.2 mg/m2) every 21 days as second-line therapy in SCLC for up to six cycles. RESULTS: Thirty patients were evaluable for response, with a response rate of 10%. Another two had an unconfirmed response. Stable disease (SD) for >or=2 cycles was seen in an additional 53%. Grade 3 or 4 non-hematologic toxicity was seen in 17 (55%) patients (26 [22%] cycles) and included fatigue, mucositis, plantar-palmar erythrodysesthesia, rash and neuropathy. Twelve patients required transfusions. All patients on study have now expired, with a median survival of 28 weeks (7 months). For patients with SD or partial response, median time to progression was 15 weeks. CONCLUSION: The combination of Caelyx, cyclophosphamide and vincristine, despite cyclophosphamide and Caelyx dose reductions, has modest activity in relapsed SCLC with acceptable toxicity.     

Phase II study of single-agent pegylated liposomal doxorubicin HCl (PLD) in metastatic breast cancer after first-line treatment failure

OBJECTIVES: Aim of this study was to evaluate the clinical benefit and the toxicity of pegylated liposomal doxorubicin. PATIENTS AND METHODS: Patients with metastatic breast cancer (n = 30) who failed a prior chemotherapy regimen for metastatic disease received 45 mg/m2 pegylated liposomal doxorubicin (PLD) every 4 weeks following prophylactic administration of metoclopramide (10 mg) and dexamethasone (8 mg). RESULTS: 29 of 30 patients were assessed for clinical benefit and time to progression. All patients were assessed for toxicity and analysis of overall survival. 9 patients (31%) had a partial response, and 16 patients (55%) responded with stable disease, resulting in a clinical benefit rate of 86% (n = 25). Median time to progression was 4 months (95% CI: 2.8-5.2), median duration of response was 7 months (95% CI: 4.7-8.2), and median survival was 12 months (95% CI: 6.7-17.2). Skin toxicity was the most common adverse event (30%, all < or = grade 2). Other toxicities were remarkably low in occurrence. CONCLUSION: PLD is a well-tolerated, second-line monotherapy with a high rate of clinical benefit.