VAD与VTD方案治疗初治多发性骨髓瘤的疗效分析

目的探讨VAD方案和VTD方案治疗初治多发性骨髓瘤的疗效。方法回顾性分析43例初治多发性骨髓瘤患者的治疗情况,其中VAD治疗组24例,VTD治疗组19例。结果 VAD治疗组有效率62.5%（15/24）,VTD治疗组有效率68.4%（13/19）,两治疗组疗效差异无统计学意义（P〉0.05）。不良反应中,心脏毒性发生率VAD治疗组高于VTD治疗组,差异有统计学意义（P〈0.05）。结论对于伴有心脏功能异常的初治多发性骨髓瘤患者应首选VTD方案治疗。     

沙利度胺联合地塞米松诱导治疗初诊多发性骨髓瘤

背景与目的:沙利度胺是治疗复发、难治性多发性骨髓瘤(multiple myeloma,MM)的有效药物,但其在初诊MM诱导治疗中的作用仍不清楚.本研究目的是评价沙利度胺联合地塞米松(thalidomide and dexamethasone,TD)在初诊MM诱导治疗中的治疗效果和不良反应.方法:应用TD方案诱导治疗39例初诊MM.沙利度胺100～300 mg/d,持续口服;地塞米松20～40 mg/d,在奇数疗程的第1～4天、第9～12天和第17～20天口服;在偶数疗程的第1～4天使用,28天为1疗程.并以36例接受VAD方案诱导治疗的临床资料匹配的初诊MM作为历史对照,比较两组的疗效、生存情况和不良反应.结果:TD方案诱导治疗初诊MM的总有效率为71.8%,VAD组为61.1%(P＞0.05).TD组中位无疾病进展生存时间(progression-free survival,PFS)为14个月,VAD组的中位PFS为9个月,两组相比差异无统计学意义(P＞0.05).TD组的中位总生存时间(overall survival,OS)尚未达到,VAD组中位OS为29个月.TD组常见的不良反应有便秘、乏力、头晕、嗜睡等,多为2级以下.VAD组3级以上白细胞减少和血小板降低明显多于TD组(P＜0.05),各种感染的发生率也高于TD组(P＜0.05).结论:TD方案是对初诊MM有效的治疗方案,可以代替VAD方案作为初诊MM的诱导治疗方案.     

Etoposide, dexamethasone, cytarabine, and cisplatin in vincristine, doxorubicin, and dexamethasone-refractory myeloma

Based on remarkable activity in refractory lymphomas, a combination of etoposide, cisplatin (both administered by 4-day continuous infusions), cytarabine (Ara-C), and dexamethasone (EDAP) was evaluated in 20 patients with advanced myeloma refractory to standard melphalan and prednisone (MP) and/or vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and dexamethasone (VAD) and even to high doses of melphalan (HDM) (seven patients). Forty percent of patients responded regardless of previously recognized risk factors (eg, duration of drug resistance, tumor mass, and serum lactic dehydrogenase [LDH] level). While the median survival was only 4.5 months, patients with good performance (Zubrod less than 2) and low or intermediate tumor stage survived more than 14 months compared with only 2 months for the remaining group. EDAP could be readily administered in the outpatient clinic, but neutropenic fever prompted hospital admission in 80% of patients, half of whom developed penumonia and sepsis, a fatal outcome in four patients. Severe myelosuppression was of short duration, so that subsequent cycles could be administered every 3 to 4 weeks. No serious extramedullary toxicity, including renal toxicity, was encountered. Marrow toxicity and hence infectious complications may be reduced by elimination of Ara-C without compromising treatment efficacy. We conclude that the lack of cross-resistance with VAD and even HDM makes EDAP or a similar combination an attractive regiment to be formally explored in an alternating sequence with VAD in high-risk myeloma.     

High-dose melphalan versus busulfan, cyclophosphamide, and etoposide as preparative regimens for autologous stem cell transplantation in patients with multiple myeloma

High-dose chemotherapy (HDC) with autologous stem cell transplant (ASCT) has improved response rates and survival for patients with multiple myeloma (MM). We report a single-institution experience using two conditioning regimens, busulfan, cyclophosphamide, and etoposide (BCV) or high-dose melphalan (HDM). Between July 1992 and August 2003, 110 patients with MM (median age=56.1) underwent HDC with ASCT using either BCV (n=62) or HDM (n=48) in sequential cohorts as the preparative regimen. Overall response rates, progression-free survival, and median overall survival were similar. BCV and HDM confer similar long-term outcomes with similar toxicity profiles as conditioning regimens prior to autologous stem cell transplant in patients with MM.     

A combination of mitoxantrone, etoposide and prednisone in elderly patients with non-Hodgkin's lymphoma.

From January 1988 to December 1991, 55 elderly patients (14 pretreated and 41 previously untreated) with non-Hodgkin's lymphoma (NHL) entered a prospective study to evaluate the feasibility of a combination of mitoxantrone (7-9 mg/m2), VP 16-213 (150 mg, 2-hour infusion on day 1, and 200 mg per os on days 3 and 5) and low-dose prednisone (25 mg days 1-5) (MVP regimen), recycling every 21-28 days. The median age was 75 (range 64-93). All but 4 pretreated patients had intermediate- or high-grade lymphomas. Complete remissions were obtained in 22 of 40 (55%) evaluable previously untreated patients, and partial remissions in 10 (2 of these obtained complete remissions after radiotherapy), for an overall response rate of 80%. The median duration of response was 12 months. At 24 months the overall survival was 52% and the relapse-free survival was 31%. Of 14 pretreated patients complete remissions were obtained in 4 (29%) and partial remissions in 3. Granulocytopenia and fever were the most important side effects; two patients contracted bronchopneumonia and one of them died. Other toxicities were mild. We conclude that this combination chemotherapy is effective as first-line and salvage treatment in elderly patients with intermediate- and high-grade NHL, and that it is feasible on an outpatient basis, with manageable toxicity.     

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。     

A Phase II trial of pegylated liposomal doxorubicin,vincristine, and reduced-dose dexamethasone combination therapy in newly diagnosed multiple myeloma patients

BACKGROUND: Patients with multiple myeloma (MM) have increased bone marrow angiogenesis, a low plasma cell labeling index, and multidrug resistance (the primary cause of chemotherapy failure). MM patients receiving the vincristine, doxorubicin, and dexamethasone (VAD) regimen develop resistance and cardiac and steroid toxicity. Pegylated liposomal doxorubicin (Doxil/CAELYX) could potentially extend the duration of malignant plasma cell exposure to therapeutic levels of doxorubicin. This Phase II study evaluates combination pegylated liposomal doxorubicin, vincristine, and reduced-dose dexamethasone in MM patients. METHODS: Thirty-three newly diagnosed patients with MM received intravenous pegylated liposomal doxorubicin (40 mg/m(2)), vincristine (2.0 mg, Day 1), and oral or intravenous dexamethasone (40 mg per day for 4 days) every 4 weeks for six or more cycles and/or for two cycles after the best response. RESULTS: The overall response rate was 88%: 4 (12%) patients achieved a complete response, 18 (55%) a major response, and 7 (21%) a minor response. Three patients (9%) had stable and one (3%) had progressive disease. The median time to progression was 23.1 months, with 2-year and 3-year progression-free survival rates of 42% and 23%, respectively. The patient survival rate at 3 years was 67%. No patients discontinued treatment due to adverse events. Myelosuppression was manageable. The most common toxicities were Grade 3 palmar-plantar erythrodysesthesia, mucositis, and neutropenia. Only one patient experienced cardiotoxicity. CONCLUSIONS: Substituting pegylated liposomal doxorubicin for doxorubicin in the VAD regimen and reducing the dose of dexamethasone in patients with MM improve the safety profile and convenience of the treatment regimen without compromising efficacy.     

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.     

Results of a phase I/II trial adding carmustine (300 mg/m2) to melphalan (200 mg/m2) in multiple myeloma patients undergoing autologous stem cell transplantation.

Autologous stem cell transplantation (SCT) with high-dose melphalan (HDM, 200 mg/m2) is the most effective therapy for multiple myeloma. To determine the feasibility of combining carmustine (300 mg/m2) with HDM, we enrolled 49 patients with previously treated Durie-Salmon stage II/III myeloma (32M/17W, median age 53) on a phase I/II trial involving escalating doses of melphalan (160, 180, 200 mg/m2). The median beta2-microglobulin was 2.5 (0-9.3); marrow karyotypes were normal in 88%. The phase I dose-limiting toxicity was > or =grade 2 pulmonary toxicity 2 months post-SCT. Other endpoints were response rate and progression-free survival (PFS). HDM was safely escalated to 200 mg/m2; treatment-related mortality was 2% and > or =grade 2 pulmonary toxicity 10%. The complete (CR) and near complete (nCR) response rate was 49%. With a median post-SCT follow-up of 2.9 years, the PFS and overall survival (OS) post-SCT were 2.3 and 4.7 years. PFS for those with CR or nCR was 3.1 years while for those with stable disease (SD) it was 1.3 years (P=0.06). We conclude that carmustine can be combined with HDM for myeloma with minimal pulmonary toxicity and a high response rate.     

吡柔比星为主的联合化疗方案治疗多发性骨髓瘤的临床观察

目的观察吡柔比星治疗多发性骨髓瘤的临床疗效及其毒副作用。方法在VAD方案中，用吡柔比星代替阿霉素组成VTD方案治疗难治性或复发性多发性骨髓瘤20例。结果血清单株免疫球蛋白下降75％以上者7例，下降50％一75％者9例，总有效率达80％。结论吡柔比星与阿霉素疗效相似，且不良反应尤其心脏毒性明显降低，为VAD方案的广泛应用创造了条件。     

A Randomized Study of MOD Versus VAD in the Treatment of Relapsed and Resistant Multiple Myeloma

67 patients with relapsed or resistant multiple myeloma were randomized to receive either VAD (vincristine, doxorubicin, dexamethasone) or MOD (mitozantrone, vincristine, dexamethasone). 12/30 (40%) patients receiving VAD and 15/37 (41%) patients receiving MOD achieved plateaux. The median duration of plateaux was significantly longer on VAD (15 months) than on MOD (8 months). No significant difference in overall survival was seen between the two treatment arms. The only toxicity which was severe in more than 5% of treatment cycles on either treatment arm was myelosup-pression. No toxicity was significantly more severe on MOD than VAD. However, hair loss was significantly more severe on VAD than MOD. The frequencies of thrombocytopenia, haematuria and cutaneous toxicity were significantly greater on VAD than on MOD. Raised serum direct bilirubin levels were seen significantly more often on MOD than VAD. MOD and VAD have similar efficacy in relapsed/resistant multiple myeloma. MOD is the less toxic of the two regimens.     

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.     

Treatment of metastatic malignant melanoma with cisplatin plus tamoxifen

 A phase II study was performed to assess the efficacy and toxicity of the combination of cisplatin (CDDP) and tamoxifen (TAM) in patients with metastatic malignant melanoma (MM). A total of 31 consecutive previously untreated patients with unresectable measurable MM were given 100 mg/m² CDDP every 21 days and 60 mg TAM every 12 h daily. All courses were given on an outpatient basis. A total of 119 courses of treatment were given. In all, 5 of the 31 patients (16%) had an objective response (95% confidence interval 5.3 – 34%) and 2 (6%) achieved a clinical complete response. The median duration of response was 7 months. The main side effect was gastrointestinal: 13% of the patients experienced grade 3/4 nausea/vomiting. Hematological or neurological toxicities were mild and rare. In conclusion, the combination CDDP-TAM has limited activity in MM, although its toxicity is tolerable. Our results do not allow us to recommend its use for the treatment of MM. Received: 27 August 1995 / Accepted: 15 November 1995     

Phase II trial of the pegylated liposomal doxorubicin in previously treated metastatic endometrial cancer: a Gynecologic Oncology Group study.

PURPOSE: To determine whether pegylated liposomal doxorubicin (PLD) has antitumor activity in pretreated patients with persistent or recurrent endometrial carcinoma and to define the nature and degree of toxicity of PLD. PATIENTS AND METHODS: Women with histologically documented recurrent or persistent measurable endometrial carcinoma and with failure of one prior treatment regardless of prior anthracycline therapy were enrolled. PLD was administered intravenously over a 1-hour period at a dose of 50 mg/m(2) every 4 weeks; the dosage was modified in accordance with observed toxicity. RESULTS: Of 46 patients entered, 42 were assessable for response, as three were declared ineligible on central pathology review and one was not assessable for response. Forty had received prior chemotherapy, 11 hormonal therapy, and 29 radiation therapy. Doxorubicin had been given to 32 patients, carboplatin with paclitaxel to six, carboplatin to one, and fluorouracil to one. Four patients had partial responses lasting 1.1, 2.1, 3.3, and 5.4 months; the overall response rate was 9.5% (95% confidence interval, 2.7% to 22.6%). Three of these responses (in liver and in lymph node) occurred in patients who had progressed after doxorubicin with either paclitaxel or cisplatin. The median number of courses was 2.5 (range, one to 14). Toxicity was generally mild: only 25 patients experienced leukopenia, with a median WBC count of 2,900 (range, 800 to 3,900) at nadir. The only grade 4 toxicities were one episode each of esophagitis, hematuria, and vomiting. The median overall survival was 8.2 months. CONCLUSION: PLD has only limited activity in pretreated advanced, recurrent endometrial cancer, but further trials in anthracycline-naive patients and in previously untreated patients are ongoing. Its toxicity profile should permit its use in combination with myelosuppressive drugs.     

多发性骨髓瘤患者血清VEGF和TNF-α及IL-6表达与沙利度胺联合化疗相关性研究

目的:探讨血清血管内皮生长因子(VEGF)、肿瘤坏死因子α(TNF-α)及白细胞介素-6(IL-6)在沙利度胺联合VAD方案化疗的多发性骨髓瘤(MM)患者中的表达及临床意义.方法:将46例MM患者随机分为T-VAD组(23例)和VAD组(23例),T-VAD组患者应用VAD方案同时连续口服沙利度胺200～250 mg/d联合化疗,共6个周期.VAD组患者行VAD方案化疗,共6个周期.用ELISA方法检测惠者治疗前后血清VEGF、TNF-α和IL-6水平.并以26例健康人作正常对照组.结果:VAD组和T-VAD组患者治疗前血清VEGF、TNF-α和IL-6水平较正常对照组均显著升高,两组差异无统计学意义(P＞0.05),与正常对照组比较差异有统计学意义,P＜0.01;治疗后两组患者血清VEGF、TNF-α和IL-6水平对照差异有统计学意义(P＜0.05),T-VAD组较VAD组下降更明显;两组治疗前后VEGF、TNF-α和IL-6水平差异均有统计学意义,P＜0.05.T-VAD组总有效率明显高于VAD组,P＜0.05.结论:MM患者血清VEGF、TNF-α和IL-6水平较正常人明显升高,T-VAD组治疗后总有效率明显高于VAD组,且T-VAD组较VAD组治疗后血清VEGF、TNF-α和IL-6水平下降更明显,对改善多发性骨髓瘤患者预后有重要作用.     

VAD chemotherapy--toxicity and efficacy--in patients with multiple myeloma and other lymphoid malignancies

Thirty-three patients with multiple myeloma (11 untreated, 15 refractory and seven relapsed patients) have received vincristine and adriamycin infusion therapy with oral dexamethasone (VAD). The median number of course received was five. In addition 16 patients with lymphoid malignancy have received a median of four courses of VAD. Three patients who relapsed after VAD have received further VAD therapy making 52 patient treatments assessable for toxicity. Ten per cent had nausea, 4 per cent vomiting, 4 per cent total alopecia, 25 per cent constipation, 33 per cent paraesthesiae, 8 per cent proximal myopathy, 33 per cent dyspepsia, 23 per cent proven bacteraemia, and 19 per cent chest infections. Infections were not usually associated with neutropenia. Shingles was seen in four patients with myeloma, but none of the patients with lymphoid malignancy. The response rate in myeloma was 9/11, for previously untreated patients, 3/7 for relapsed, and 8/15 for refractory patients. Responses have been seen in other lymphoid malignancies-1/2 patients with relapsed acute lymphoblastic leukaemia had a complete remission. Two out of seven patients with chronic lymphocytic leukaemia achieved a partial remission, and a further three had a clinical improvement. Three out of six patients with non-Hodgkin lymphoma and one patient with macroglobulinaemia achieved a partial remission.     

High-dose busulfan in patients with myeloma.

PURPOSE: To evaluate the use of high-dose busulfan (HDB) with autologous bone marrow transplantation (ABMT) in patients with myeloma. PATIENTS AND METHODS: Fifteen patients received HDB (16 mg/kg), eight of whom received high-dose melphalan (HDM) but had experienced a short remission or progression-free interval. Two patients had received HDM on two previous occasions, one had no response to low-dose melphalan, and four had impaired renal function (edathamil clearance < 40 mL/min). All patients received induction chemotherapy before HDB. RESULTS: Two patients were in complete remission (CR) after induction chemotherapy before HDB. Of the remaining 13 patients, four (31%) achieved CR and two (15%) achieved a partial remission for an overall response rate of 46%. There were three treatment-related deaths, but the toxicity was otherwise predictable and manageable. CONCLUSIONS: In heavily pretreated patients, HDB results in a relatively high response rate. It can also be used safely in patients with renal impairment who are not suitable for HDM.     

A new protocol (MiCEP) for the treatment of intermediate or high-grade non-hodgkin's lymphoma in the elderly

Age has proved to be an important prognostic factor in patients with advanced non-Hodgkin lymphoma (NHL) and these patients require intensive and extensive therapy. Dose-reduction and therapy attenuation have reduced treatment-related toxicity, but have also decreased therapeutic efficacy.

Between January 1990 and December 1992, 41 previously untreated patients, 65 years with stage 2-4 intermediate- or high-grade NHL were treated with a new therapeutic scheme which included Mitoxantrone, Etoposide, Cyclophosphamide and Prednisone (MiCEP). Twenty-eight patients achieved a complete remission, ten patients partial remission (overall response rate of 93%) and two cases were resistant. The overall survival was 66% with a median follow-up of 24 months from diagnosis: three patients relapsed after a median period of 7 months. The relapse-free survival was 92% after a median follow-up of 18 months. Blood and other organ toxicity was acceptable and 12% of patients experienced a grade 4 (WHO) neutropenia. In conclusion, MiCEP was effective in inducing a good remission rate with moderate toxic effects in elderly patients with intermediate- or high-grade NHL and appears to be a useful combination to use in this group of patients.     

Prospective evaluation of coagulopathy in multiple myeloma patients before, during and after various chemotherapeutic regimens

BACKGROUND: Venous thromboembolism (VTE) occurs frequently in multiple myeloma patients, especially during induction treatment with thalidomide in combination with anthracyclines and/or dexamethasone. Several coagulation abnormalities have been described in untreated myeloma patients, but these have not been prospectively evaluated during and after treatment. PATIENTS AND METHODS: We performed a prospective study in 138 multiple myeloma patients in whom coagulation factor levels were evaluated longitudinally before, during induction and after intensification. Patients were randomized to induction treatment consisting of adriamycin and dexamethason, in combination with either vincristin (VAD), thalidomide (TAD), or bortezomib (PAD) followed by high-dose melphalan (HDM) and autologous stem cell transplant (ASCT). RESULTS: Factor VIII:C (FVIII:C) and von Willebrand factor (VWF) were significantly elevated before treatment (median FVIII:C 2.26U/ml, VWF:Ag 1.95 U/ml). Irrespective of the type of induction regimen, these variables increased strongly during induction therapy (FVIII:C 2.55 U/ml and VWF:Ag 2.96 U/ml). Fibrinogen also showed a significant increase after induction therapy (3.5 g/l pre-treatment and 4.0 g/l after treatment, respectively, P<0.001). This was significantly higher in TAD than VAD treated patients. Three to six month after ASCT levels of VWF and FVIII:C had decreased to values lower than observed before treatment (1.71 and 1.67 U/ml respectively). There was no correlation between the increased levels at start and the response of multiple myeloma to treatment. High levels of VWF, fibrinogen and FVIII:C before start of treatment were significantly associated with mortality. Fourteen patients (10%) developed a venous thrombotic event (VTE). The coagulation factor abnormalities before and during treatment were not associated with the development of VTE. CONCLUSION: During induction treatment several changes in coagulation factor levels are observed, which may result in a prothrombotic state. Larger studies are required to establish whether the changes in these coagulation factors during induction treatment contribute to the increased risk of venous thromboembolism in multiple myeloma patients.     

Pegylated liposomal doxorubicin, melphalan and prednisone therapy for elderly patients with multiple myeloma

Melphalan & Prednisone (MP) is considered as the standard therapy for Multiple Myeloma (MM) patients not eligible for high-dose therapy. Here, we report the results of a phase I-II study to evaluate the feasibility and efficacy of the association of PLD to the conventional MP regimen during the first six cycles of the front-line therapy for untreated MM patients older than 70. Thirty patients were included in the study with a median age of 77 years (71-84) and a M/F ratio of 17/13. The phase I of the study demonstrated that the maximum tolerable dose of PLD in this setting was 30 mg/m(2), so it was the final dose evaluated in the study. Twenty-nine patients were valuable for response, which was: complete in 4 (14%) partial in 15 (52%) minor/no changes in 7 (24%) and progressive in 3 (10%). The median progression free survival (PFS) was 24 months. The median overall survival (OS) has not been reached yet, with a 3-year probability for OS and PFS of 52 and 37%, respectively. Haematological toxicity was frequent but usually weak/moderate (grades 1 & 2 of the WHO scale) and it was resolved only with dose delays. Infection was a relatively frequent event (30% of patients), but only in 4 cases it was of grade 3. No cases of palmar-plantar erythrodysesthesia were observed. In conclusion, pegylated liposomal doxorubicin can be safely added to the other chemotherapeutic drugs in the treatment of elderly MM patients, which can be very useful for patients in whom novel agents are not tolerated or inefficient.