沙利度胺、马法兰联合地塞米松治疗多发性骨髓瘤疗效观察

目的观察沙利度胺、马法兰联合大剂量地塞米松治疗多发性骨髓瘤的疗效。方法12例多发性骨髓瘤患者均采用沙利度胺50～200mg/d口服,马法兰6mg/d,服1周停3周余,同时联合大剂量地塞米松40mg/d、用4d停4d、20d后停10d,1月后重复,治疗3个月,有6例加用了粒细胞刺激因子。结果完全缓解（CR）3例,部分缓解（PR）4例,进步4例,无效1例,不良反应均可耐受。有效率达91.7%。结论沙利度胺、马法兰联合大剂量地塞米松治疗多发性骨髓瘤安全有效,疗效高且经济耐受性好。     

Outcomes Following Isolated Limb Infusion for Melanoma. A 14-Year Experience

Background  Isolated limb infusion (ILI) is a minimally invasive technique for delivering regional chemotherapy in patients with advanced and metastatic melanoma confined to a limb. It is essentially a low-flow isolated limb perfusion (ILP) performed via percutaneous catheters without oxygenation. Methods  From our prospective database 185 patients with advanced metastatic melanoma of the limb treated with a single ILI between 1993 and 2007 were identified. In all patients a cytotoxic drug combination of melphalan and actinomycin-D was used. Drug circulation time was 20–30 min under mild hyperthermic conditions (38–39°C). Results  The majority of patients (62%) were female. Their average age was 74 years (range 29–93 years). Most patients had MD Anderson stage III disease (134/185). The overall response rate was 84% [complete response (CR) rate 38%, partial response rate 46%]. Median response duration was 13 months (22 months for patients with CR; P = 0.01). Median follow-up was 20 months and median survival was 38 months. In those patients with a CR, the median survival was 53 months (P = 0.005). CR rate and survival time decreased with increasing stage of disease. On multivariate analysis significant factors for a favorable outcome were achievement of CR, stage of disease, thickness of primary melanoma, the CO₂ level in the isolated circuit, and a Wieberdink limb toxicity score of III (considerable erythema and edema). Conclusion  The response rates and duration of response after ILI are comparable to those achieved by conventional ILP. ILI is a minimally invasive alternative to the much more complex and morbid conventional ILP technique for patients with advanced metastatic melanoma confined to a limb.     

Idiopathic thrombocythemia and pregnancy; a case report

A 28-year-old woman with idiopathic thrombocytosis was treated with melphalan before pregnancy, which resulted in a normal platelet count. During pregnancy 80 mg acetylsalicylic acid was given daily to prevent microcirculatory thrombotic complications. Fetal outcome was normal.     

肿瘤细胞体外耐药与体内化疗疗效关系的实验研究

目的通过动物实验探讨恶性肿瘤体内化疗的疗效与肿瘤细胞体外药物敏感性预测的关系。方法采用浓度梯度递增法制备小鼠淋巴瘤EIA耐药细胞系EIA／美法仑,四甲基偶氮唑蓝（MTT）比色法检测其在体外对美法仑的耐药指数。利用单一剂量化疗药物治愈荷瘤小鼠的动物模型,将等量EIA／美法仑和EIA细胞分别接种在野生型C57BL／6小鼠皮下,接种后12d,荷EIA／美法仑肿瘤小鼠和荷EIA肿瘤小鼠分别再随机分为美法仑治疗组和对照组,每组各5只。美法仑治疗组荷瘤小鼠腹腔内单次注射7．5mg／kg的美法仑,对照组荷瘤小鼠腹腔内注射等量生理盐水。随后观察各组荷瘤小鼠肿瘤结节直径的变化。结果EIA／美法仑耐药细胞和EIA细胞形态上肉眼无明显区别,EIA／美法仑细胞可在含5μg／ml美法仑的培养基中长期存活,其对美法仑的耐药指数为2．87。动物体内实验发现7．5mg／kg美法仑不仅能使荷EIA肿瘤小鼠的肿瘤结节消退,而且也能使荷EIA／美法仑肿瘤小鼠的肿瘤治愈。结论恶性肿瘤体内化疗的疗效与肿瘤细胞在体外是否对该化疗药物耐药无关,在体外对美法仑耐药的肿瘤细胞对美法仑的体内治疗仍敏感。     

The effect of treatment with high dose melphalan,cisplatin or carboplatin on levels of glutathione in plasma,erythrocytes, mononuclear cells and urine

 Glutathione (GSH) has been implicated as an important factor in the detoxification of many electrophilic xenobiotics, including agents used in cytotoxic chemotherapy. Maintenance of high levels of GSH in normal tissues is believed to be important in the prevention of drug-induced toxicity. Previous studies have indicated that exposure of cells to some toxic electrophiles both in vitro and in vivo can cause a temporary decrease in intracellular levels of GSH. In this paper we report that in a series of 22 children and young adults treated with high dose melphalan (ten courses studied, all 200 mg/m²), cisplatin (eight courses, 80–104 mg/m²) or carboplatin (seven courses, 507–750 mg/m²) there was no significant alteration in the level of plasma, erythrocyte or urine GSH in the period immediately following drug administration. Fluctuations in the level of GSH in mononuclear cells were observed in some patients but did not follow any consistent pattern and were similar to those observed in a series of nine normal adult controls over the same time course. These results suggest that for melphalan, cisplatin and carboplatin, drug-GSH adduct formation is insufficient to cause a measurable decrease in intracellular GSH levels in normal peripheral haematopoietic cells during the course of treatment. Received: 6 October 1994/Accepted: 22 May 1995     

Potentiation of melphalan activity in the KHT sarcoma by the radiosensitizer RSU 1069

The radiation sensitizer misonidazole (MISO) has been shown to potentiate the cytotoxic action of a variety of anti-cancer agents. Even larger enhancement ratios than those observed with MISO have been found with certain other nitroimidazoles. One agent reported to be particularly effective in combination with the chemotherapeutic agent melphalan is the sensitizer RSU 1069. The present studies therefore were designed to evaluate the effect of combining these two agents in the treatment of intramuscularly growing KHT sarcomas. Tumor response was assessed using an in vivo to in vitro clonogenic cell survival assay. When given at times ranging from 60 min before to 30 min after melphalan exposure, RSU 1069 was found to increase the tumoricidal activity of the chemotherapeutic agent. Complete dose response curves combining RSU 1069 and a range of melphalan doses then were determined. For comparison the effects of combining MISO or benznidazole (BENZO) with melphalan also were evaluated. All sensitizers were administered i.p. either 30 min before (BENZO) or simultaneously with (MISO, RSU 1069) the chemotherapeutic agent. Survival of clonogenic tumor cells assessed 22 to 24 hr after treatment was used to assay tumor response. When combined with melphalan, doses of RSU 1069 (0.38 mmol/kg), BENZO (0.3 mmol/kg) and MISO (5.0 mmol/kg) were found to yield dose modifying factors of 1.6, 1.5, and 1.4, respectively. These results indicate that potentiation of melphalan activity occurs at RSU 1069 doses which are approximately 10-fold lower than those of MISO, making this sensitizer as effective a potentiator of melphalan as so far tested in the KHT sarcoma.     

Isolated Limb Perfusion With Tumor Necrosis Factor α and Melphalan for Locally Advanced Soft Tissue Sarcoma: The Value of Adjuvant Radiotherapy

Background The aim was to investigate the value of adjuvant radiotherapy for locally advanced soft tissue sarcoma after hyperthermic isolated limb perfusion (ILP) with tumor necrosis factor α and melphalan followed by limb-saving surgery. Methods From 1991 to 2003, 73 patients (median age, 54 years; range, 14–80 years) underwent 77 ILPs, followed by resection in 68 patients (93%). Radiotherapy was administered in case of marginally or microscopically positive resection margins. Local recurrences were scored and calculated according to the Kaplan-Meier method and log-rank test. Results After residual tumor mass resection, 58% received radiotherapy (external beam radiotherapy [EBRT]⁺ group), and 42% did not (EBRT⁻ group). The median follow-up was 28 months (range, 2–159 months). A significantly better local control rate was observed in the EBRT⁺ compared with the EBRT⁻ group (P < .0001). When only R0 resections in patients without metastasis were considered, the significance remained between groups (P = .0003). In the EBRT⁻ group, an R1 or R2 resection resulted in earlier relapse of local disease compared with R0 resections (P = .0475). Conclusions Adjuvant EBRT reduces the risk for local recurrence after delayed resection in soft tissue sarcoma patients treated with ILP and tumor necrosis factor and is indicated when resection margins are close or microscopically positive. It also seems beneficial after an R0 resection.     

Treatment of multiple myeloma: a randomized study of three different regimens

The results of an Italian multicentric trial for treatment of symptomatic Multiple Myeloma (MM) are reported. One hundred and thirty-three previously untreated patients were singled out at random for three different chemotherapy schedules: Melphalan plus Prednisone (M.P.) X 6 monthly cycles; Vincristine plus Melphalan plus Cyclophosphamide plus Prednisone (VMCP) X 6 monthly cycles; Peptichemio, Cyclophosphamide, BCNU. Drugs in this latter schedule were administered sequentially, for a period of six months. Criteria for response, progression and relapse were those of the Southwestern Oncology Group. Fifteen patients in MP chemotherapy (35%) and 20 patients in VCMP chemotherapy (46%) achieved an objective response (decrease of at least 50% in the synthesis index of Monoclonal Component (M.C.], while only 3 out of the other 21 patients assigned to the third schedule responded to treatment. No significant differences were noted in the survival curves in either of the three treatment groups. The 38 responding patients did not receive maintenance therapy; no significant difference was found in remission duration between patients in MP and VCMP arms, with a median duration of 16 months for the whole group. No statistical difference was observed between survival and remission curves of patients with a 'response' (M. spike reduction greater than 75%) and those with 'improvement' (M. spike reduction between 75 and 50%). The authors conclude that the inclusion of Vintristine in a combination chemotherapy does not produce clear survival benefits; a longer induction period (12 cycles) could allow a better differentiation between MP and VMCP regimens.     

Treatment of Bendamustine and Prednisone in patients with newly diagnosed multiple myeloma results in superior complete response rate, prolonged time to treatment failure and improved quality of life compared to treatment with Melphalan and Prednisone—a randomized phase III study of the East German Study Group of Hematology and Oncology (OSHO)

Purpose: This randomized phase III study compared bendamustine and prednisone (BP) to standard melphalan and prednisone (MP) treatment in previously untreated patients with multiple Myeloma (MM). Patients and Methods: To be included, patients had to have histologically and cytologically proven stage II with progressive diseases or stage III MM. They were randomly assigned to receive BP (n=68) or MP (n=63). The primary endpoint was the time to treatment failure (TTF). Secondary endpoints included survival, remission rate, toxicity and quality of life. Results: The overall response rate was 75% in the BP and 70% in the MP group. A significantly higher number of patients treated with BP achieved a complete remission than did patients receiving MP (32 vs. 13%; P=0.007), and the maximum response was achieved more rapidly in patients treated with BP compared to those receiving MP (6.8 vs. 8.7 cycles; P<0.02). TTF and remission duration were significantly longer in the BP group. Patients receiving BP had higher QoL scores and reported pain less frequently than patients receiving MP. Conclusion: BP is superior to MP with respect to complete remission rate, TTF, cycles needed to achieve maximum remission and quality of life and should be considered the new standard in first-line treatment of MM patients not eligible for transplantation.