博莱霉素联合顺铂治疗恶性胸水的临床观察

目的观察抗肿瘤抗生素博莱霉素联合顺铂治疗恶性胸水的疗效.方法本组恶性胸水患者36例,治疗组20例,行博莱霉素加顺铂治疗;对照组16例,行丝裂霉素加顺铂治疗.结果治疗组总有效率为95.0%,对照组为81.3%(P<0.05).治疗组Karnofsky评分高于对照组.主要不良反应为发热.结论博莱霉素治疗恶性胸水疗效确切,在改善生存质量方面优于丝裂霉素,且不良反应少,可作为恶性胸水胸腔灌注治疗的首选.     

Treatment of metastatic malignant melanoma with 24 hours continuous venous infusion of dacarbazine and cisplatin

Twenty consecutive patients with metastatic malignant melanoma were treated with a combination of 24 hours continuous infusion of dacarbazine (250 mg/m2) and cisplatin (20 mg/m2) for 5 days every 3 weeks. One patient (5%) achieved a complete response (CR) and 3 patients (15%) obtained a partial response (PR) with an overall response rate of 20%. Minimal response was observed in 5 other patients (25%). Complete response duration was 8 months. Median response duration of partial responders was 7 months. Median survival of all responders (CR+PR) was 8.5 months. Toxicity was mild to moderate.     

恶性黑色素瘤化疗研究进展

恶性黑色素瘤(Malignant melanoma,MM)是一种恶性程度极高的实体肿瘤,它极具侵袭性,预后差。尽管晚期黑色素瘤的治疗已经进入靶向和免疫治疗的时代,但是化疗仍然不可摒弃。恶性黑色素瘤的化疗经历了从单药化疗、两药或三药甚至四药的联合化疗、再到生物化疗这一发展过程。本文综述恶性黑色素瘤化疗研究进展,对主要的化疗方案进行比较,展望化疗未来发展的方向。     

Treatment of metastatic malignant melanoma with dacarbazine plus tamoxifen,or vindesine plus tamoxifen: a prospective randomized study

This study aimed to verify whether the advantage in terms of response rate and survival of dacarbazine plus tamoxifen over dacarbazine alone in metastatic malignant melanoma reported in a previous randomized trial was due to a specific interaction of dacarbazine with tamoxifen. A total of 125 patients with locoregional or disseminated malignant melanoma were randomized to receive dacarbazine (250 mg/m(2) days 1-5 every 3 weeks) plus tamoxifen (arm A) or vindesine (3 mg/m(2) every week for 6 weeks, then every 2 weeks) plus tamoxifen (arm B). Of the 125 randomized patients, 57 and 59 were evaluable in arm A and B, respectively. The complete response rates were the same (2% versus 2%) and the complete plus partial response rates were similar (11% versus 14%) in the two groups. There was no significant difference in survival. Neither response or survival correlated with gender. In conclusion, when combined with tamoxifen, dacarbazine does not have a specific effect on response or survival compared with vindesine. The lower response rate to dacarbazine plus tamoxifen (11%) than that reported in the previous trial (28%) might be explained by actual differences in patient and/or participating centre accrual characteristics in the presence of apparently identical eligibility criteria.     

Thiotepa and etoposide treatment of recurrent malignant gliomas: phase I study

 Purpose: To determine: (1) the maximum tolerable dose (MTD) of thiotepa (TT) that can be administered with etoposide without stem cell support; (2) whether this regimen is active against recurrent malignant gliomas. Background: Although several chemotherapeutic agents show minor activity against recurrent brain tumors, there is no consensus about the most effective regimen. The alkylating agent TT has excellent central nervous system (CNS) penetration and is synergistic with the topoisomerase II inhibitor etoposide. Design/Methods: Fifteen patients with recurrent malignant gliomas (14 glioblastomas, 1 anaplastic astrocytoma) received intravenous etoposide 100 mg/m² on days 1, 2, and 3, and intravenous TT (40, 50, 60, or 70 mg/m²) on day 2. All had received irradiation, and eight BCNU. Chemotherapy was repeated every 3 – 4 weeks, with stepwise TT dose increments of 10 mg/m², provided toxicity was less than grade III. Results: The major toxicity was dose-limiting leukopenia. The MTD of TT in cycle 1 was 60 mg/m². All patients died of progressive disease and none died of chemotherapy-related complications. Conclusions: The MTD of TT in this regimen for recurrent malignant gliomas is 60 mg/m². Higher doses of TT would require colony-stimulating factors or stem cell support. Received: 14 March 1995 / Accepted: 5 September 1996     

Cutaneous matastasis from sino-nasal malignant melanoma — a rare case report

To report a case of disseminated cutaneous metastasis from malignant melanoma of sino-nasal region. A 53-year-old man from rural parts of West Bengal presented with progressive nasal obstruction. CT scanning was done to know the extent of the mass and punch biopsy from the mass was performed. Malignant melanoma of sino-nasal region was diagnosed and chemotherapy was started. The patient developed cutaneous deposits after two cycles of chemotherapy. The patient developed cutaneous deposits during the course of chemotherapy. Excision biopsy from cutaneous deposits revealed malignant melanoma. A rare case of diffuse cutaneous metastasis of malignant melanoma is presented here along with review of literature.     

胞必佳联合顺铂治疗恶性胸腔积液的临床研究

目的：评价胞必佳联合顺氯氨铂治疗恶性胸腔积液的疗效和毒性。方法：６０例恶性胸腔积液患随机分为两组,Ａ组单用胞必佳治疗,Ｂ组：胞必佳＋顺氯氨铂（ＤＤＰ）。结果：在治疗后头４个月,两组完全缓解率没有明显差异,但在治疗后６个月,Ｂ组的完全缓解率明显高于Ａ组,有明显差异性,不良反应主要为胃肠道反应、胸痛和低热,较轻,对症处理可缓解。结论：胞必佳联合顺氯氨铂治疗恶性胸腔积液的疗效明显高于单药胞必佳的治疗效果。     

Weekly Cisplatin during cranial irradiation for malignant melanoma metastatic to brain

Because Cisplatin potentiates the effect of radiotherapy in animal tumor systems and because Cisplatin is capable of causing regressions of human malignant melanomas, a study was initiated in patients with malignant melanoma metastatic to brain to investigate the feasibility of administering Cisplatin once a week during cranial irradiation.Cisplatin 40 mg/m²/week (three doses) was given LV. to 18 patients during whole brain irradiation, 3 000 rads in 12 fractions over 2 1/2 weeks. Eleven patients also received Cisplatin 120 mg/m² every three weeks, starting three weeks after cranial irradiation. Median survival was ten weeks, and only one of 13 patients whose brain metastases had not been resected experienced neurological and CT scan improvement. Thirteen patients have died, and brain metastases were a major cause. No regression of extracerebral tumor was seen in 15 patients with eveluable extracerebral lesions. During weekly low-dose Cisplatin administration, nausea and vomiting were moderate to severe. No granulocytopenia was noted, although three courses were associated with mild thrombocytopenia. Mucositis, peri orbital swelling, vertigo, and headache were each noted in two of 51 courses of treatment and seizures, ototoxicity, pancreatitis, and hiccups were each noted in one course. Renal toxicity and ototoxicity each developed in three of the 11 patients receiving Cisplatin 120 mg/ m², and nausea and vomiting were severe.     

Treatment of metastatic malignant melanoma with dacarbazine plus fotemustine

Despite the poor prognosis of metastatic malignant melanoma, polychemotherapy with dacarbazine and fotemustine has shown promising results in several studies. We report on the clinical efficacy of a new sequential administration regimen with dacarbazine at a dose of 200 mg/m2 followed 24 h later by fotemustine 100 mg/m2 every 4 weeks in 63 patients with metastatic melanoma. A complete response was noted in 3 patients (5%), a partial response in 4 patients (6%), stable disease in 33 patients (5%) and progressive disease in 23 patients (37%). The duration of the 3 complete responses was 5, 14+ and 60+ months, for the 4 partial responses, 3, 4, 6 and 13 months. The median duration for stable disease was 4 months. The best response rates were obtained for lung and lymph node metastases. Toxicity was mild and mainly limited to haematological without pulmonary side-effects. Although there was a relatively low objective response rate, this chemotherapy regimen as a palliative treatment, is potentially valuable for patients with progressive stage IV melanoma.     

盖诺加顺铂联合治疗中晚期恶性肿瘤39例疗效观察

目的 :观察并评价国产长春瑞宾 (盖诺 )加顺铂联合 (NP方案 )治疗中晚期恶性肿瘤的疗效。方法 :39例均为病理或临床确诊为中晚期恶性肿瘤。予以盖诺 2 5～ 30mg/m2 ,静脉滴注 ,d1,d5 ;顺铂 2 5～ 30mg/m2 ,dl,d2 ,d3,静脉滴注。 2 1天～ 2 8天为 1周期 ,连续 2～ 4周期 ,观察化疗疗效及毒副反应。结果 :39例中 :CR4例 (10 3% ) ,PR18例 (46 2 % ) ,NC15例(38 5 % ) ,PD2例 (5 1% )。毒副反应主要是骨髓抑制 ,其次是静脉炎症。结论 :盖诺加顺铂治疗中晚期恶性肿瘤疗效确切 ,只要处理得当 ,毒副反应可以耐受     

Chronic inflammatory demyelinating polyneuropathy associated with metastatic malignant melanoma of unknown primary origin

Paraneoplastic neurological syndromes (PNS) are rare manifestations of malignant disease. It is currently believed that most, if not all, PNS are autoimmune in nature. Proteins expressed on the surface of tumor cells trigger an immune response that cross-reacts with similar proteins in the nervous system, resulting in damage. Moreover, recent studies propose that the appearance of autoimmune phenomena in patients with malignant melanoma implies a strong antitumoral activity and constitutes a marker of improvement in overall survival. We describe a most unusual case of chronic inflammatory demyelinating polyneuropathy (CIDP) occurring in a patient with metastatic malignant melanoma of unknown primary origin who received treatment with interferon alpha-2b. We also review the relevant literature about this infrequent association, discuss on its pathogenesis and underline its importance as surrogate marker, useful to verify the antineoplastic treatment efficacy.     

Hyaluronidase pretreatment produces selective melphalan enrichment in malignant melanoma implanted in nude mice

 Preclinical and clinical observations suggest that the administration of hyaluronidase (Hyase) shortly before that of chemotherapy increases the access and, thus, the effectiveness of aniticancer drugs in tumors. To examine this hypothesis as well as the selectivity of such a therapeutic approach potentially beneficial in isolated limb perfusion, the Hyase-induced distribution of melphalan was measured in tumor-bearing nude mice with respect to the mode of drug administration using RP-18 ion-pair high-performance liquid chromatography (HPLC) with fluorimetric detection. Melphalan alone (50 μmol/kg) or a combination of melphalan (50 μmol/kg) and Hyase (100,000 IU/kg) was injected either i.p. or s.c. in the vicinity of the tumors. The s.c. melphalan injection caused a 4-fold rise in melphalan concentration (59 μM) in the tumors as compared with i.p. application (15 μM). Only minor effects were observed with respect to the route of melphalan application on its distribution in other tissues (ca. 13 μM in plasma, 15 μM in muscle, 30 μM in the liver, 26 μM in the kidney, and 21 μM in the testicle). Irrespective of the route of Hyase coadministration, the enzyme increased the concentration of i.p. injected melphalan in all tissues to ca. 20 μM in the tumor, 15 μM in plasma, 27 μM in muscle, 40 μM in the liver, 29 μM in the kidney, and 28 μM in the testicle. In contrast, s.c. injected melphalan was selectively accumulated by the tumors after both s.c. and i.p. Hyase administration (462 and 388 μM, respectively). Melphalan enrichment in the tumors was higher (16- to 32-fold higher than in the other tissues) after i.p. administration of Hyase since, in contrast to s.c. injection of the enzyme, its i.p. administration caused a decrease in the concentration of the cytostatic in all other tissues as compared with the s.c. administration of melphalan alone. Received: 8 May 1995/Accepted: 5 September 1995     

吉西他滨联合顺铂一线或二线治疗晚期三阴性乳腺癌的临床观察

目的　观察吉西他滨联合顺铂一线或二线方案治疗晚期三阴性乳腺癌的近期疗效和毒副反应。方法　５４例晚期三阴性乳腺癌患者接受吉西他滨联合顺铂治疗,其中一线治疗４５例,二线９例,具体方案：吉西他滨１０００ｍｇ／ｍ^２ｄ_１、ｄ_８,顺铂２５ｍｇ／ｍ^２ｄ_１～ｄ_３,２１天为１周期。每２周期评价疗效,每周期进行安全性评估。结果　５４例患者中位治疗周期数为６周期（２～８周期）,获ＣＲ８例（１４.８％）,ＰＲ２４例（４４.４％）,ＳＤ１８例（３３.３％）,ＰＤ４例（７.４％）,总有效率（ＣＲ＋ＰＲ）为５９.２％。主要毒副反应为骨髓毒性和消化道反应,３～４级毒性分别为中性粒细胞减少４０.７％,血小板减少３５.２％,乏力１８.５％,食欲下降１４.８％,贫血１１.１％,恶心呕吐９.２％,外周神经毒性１.９％。结论　吉西他滨联合顺铂治疗晚期三阴性乳腺癌近期疗效好,毒副反应可以耐受,可推荐作为晚期三阴性乳腺癌的治疗选择。     

The role of tamoxifen in combination with cisplatin on oral squamous cell carcinoma cell lines

The purpose of this study was to evaluate the effect of tamoxifen (TAM) when used in combination with cisplatin on oral squamous cell carcinoma (OSCC). For this, the relation between estrogen receptor (ER) expression level and the cytotoxic effect of TAM, the apoptotic effect and its molecular mechanisms of TAM were investigated using OSCC cell lines. Combination treatment demonstrated a superior cytotoxic and apoptotic effect on OSCC cell lines. Considerable amount of ER was detected in some OSCC cell lines, but there were no significant differences of cytotoxic effect of TAM. TAM inhibited PKC activity and up-regulated TGF-beta1 secretion.     

吉西他滨联合顺铂与去甲长春碱联合顺铂治疗晚期非小细胞肺癌的临床研究

目的 观察比较吉西他滨联合顺铂(GC方案)与去甲长春碱联合顺铂(VC方案)治疗晚期非小细胞肺癌的疗效、生存率及毒副反应。方法 对67例经病理或细胞学证实的晚期非小细胞肺癌患者给予联合化疗，GC方案32例，VC方案35例，两组病例具有可比性。吉西他滨1000～1250mg／m^2，静脉滴注第1、8天，顺铂80～100mg／m^2，静脉滴注第1～3天，去甲长春碱25mg／m^2，静脉滴注第1、8天，21天为一个周期，每例患者治疗2周期以上。结果 GC组总有效率37．5％，1年生存率38．7％，中位生存期9．5个月；VC组总有效率34．3％，1年生存率34．3％，中位生存期8．6个月。两组间有效率、1年生存率比较差异均无显著性(P=0．59，P=0．48)。最常见的毒副反应为骨髓抑制，GC组Ⅲ～Ⅳ度血小板减少发生率显著高于VC组(P=0．015)，而VC组Ⅲ～Ⅳ度白细胞减少发生率显著高于GC组(P=0．01)。结论 吉西他滨联合顺铂和去甲长春碱联合顺铂治疗NSCLC，疗效肯定，毒性均可耐受。两方案疗效无显著性差异。     

热药灌注化疗对肢端恶性黑色素瘤患者CD3+、CD4+、CD8+表达的影响

目的 探讨肢端恶性黑色素瘤区域热药灌注化疗对CD3+,CD4+,CD8+表达的影响.方法 34例肢端恶性黑色素瘤患者行区域热药灌注化疗手术,检测治疗前后CD3+,CD4+,CD8+表达,二次手术切除原发灶.结果 区域热药灌注化疗手术后肿瘤组织坏死,CD4+成高表达,CD4+/CD8+比值增加,对照治疗前后有显著性差异(P＜0.05).结论 区域热药灌注化疗手术对肢端恶性黑色素瘤可提升细胞免疫功能,防止肿瘤复发转移,并促使肿瘤组织坏死,有利于手术切除.     

Prognostic factors in metastatic malignant melanoma treated with combined radiation therapy and hyperthermia

From May 1981 to September 1991, 38 patients with metastatic malignant melanoma were treated with combined radiation therapy and hyperthermia to a total of 97 hyperthermia treatment fields. Prior treatments to these sites included surgery (31 patients, 76 fields), chemotherapy (18 patients, 54 fields), immunotherapy (14 patients, 42 fields) and radiation therapy (7 patients, 13 hyperthermia fields). Hyperthermia was given to fields located in the head and neck region, trunk and extremities in 30, 45 and 22 cases, respectively. Nodular-diffuse tumours were present in 86 fields while 11 fields were treated for microscopic residual tumour deposits. Concurrent radiation therapy was given in 180–400 cGy per fraction, 2–5 times per week for a mean total dose of 4098 cGy per field. Hyperthermia treatments were delivered using either microwave or ultrasound devices (286 and 48 treatments, respectively) with a mean (range) of 3. 4 (1–14) hyperthermia treatments per field for a mean (range) of 43 (10–70) min per field. Patients (n = 34; 84 fields) were available for follow-up for a mean (range) of 14–6 (0–4-82.5) months. At 3 weeks post-treatment, 34 fields had complete, ongoing, or partial responses; 39 fields had no response; and there were no recurrences in the 11 fields treated for microscopic residual disease. Local control was maintained in 31% (26/84) fields with a mean follow-up of 14.6 months. At 36 months, five patients remained alive with complete control of their treated local disease. Statistical analyses revealed that patients with soft tissue metastases only, who were older at the time of hyperthermia, had a longer time between initial diagnosis and hyperthermia treatment, received a higher dose of radiation, had no previous chemotherapy, and had small tumour volumes, had a higher initial response. Multivariate analyses revealed that the three-covariate model including time interval between initial diagnosis and hyperthermia treatment, previous chemotherapy, and metastases to soft tissue only, best predicted response. The results of the investigation support the continued study of combined radiation therapy and hyperthermia treatments for selected patients with metastatic melanoma, and indicate that long-term survival can occasionally be obtained with this approach.     

Treatment of metastatic malignant melanoma with dacarbazine, vindesine and cisplatin

Twenty-seven patients with disseminated malignant melanoma were treated monthly with cisplatin (CDDP) 120 mg m-2 on day 1, vindesine (VDS) 3 mg m-2 on day 2 and dacarbazine (DTIC) 250 mg m-2 on days 2-6. None of them had received prior chemotherapy. All patients are evaluable for response and toxicity. There were five (19%) complete (CR) and seven (26%) partial (PR) responses for a total response rate of 45%. We conclude that the combination of DTIC, VDS and CDDP is capable of producing a relatively high rate of response in patients with advanced metastatic malignant melanoma, but responses are short.     

Phase I study of the combination of docetaxel, temozolomide and cisplatin in patients with metastatic melanoma

Purpose  In a search for more effective combination chemotherapy for the treatment of metastatic melanoma, we conducted a phase I trial of a novel combination of docetaxel, temozolomide, and cisplatin. Methods  Patients with inoperable or recurrent metastatic melanoma with a Zubrod performance status of 2 or less and adequate organ function were eligible. The dose of docetaxel was escalated between cohorts of patients, and the doses of temozolomide and cisplatin were fixed. A standard 3 + 3 dose escalation design was used to determine the maximum tolerated dose (MTD). Results  Among 23 patients who were enrolled, 21 were evaluable for toxicity. Eighteen patients (78%) had stage IV-M1c disease. The dose-limiting toxicities were myelosuppression and pulmonary embolism. The MTD was 30 mg/m² docetaxel on days 1, 8, and 15 when given with 150 mg/m² temozolomide on days 1–5, and 20 mg/m² cisplatin on days 1–4, repeating every 4 weeks. Among 19 patients evaluated for response, 6 (32%) had partial responses and 5 (26%) had stable disease. Among 14 chemo-naive patients, 6 (43%) had a partial response and 4 (29%) had stable disease. Nine patients developed brain metastases by the time of the last follow-up evaluation, and the median time to brain metastases for all 19 evaluable patients has not been reached. Conclusions  This combination was well tolerated and appears to be a promising treatment for patient with metastatic melanoma. This study was supported by Sanofi-Aventis.     

VP-16联合DDP心包腔内注射治疗非小细胞肺癌恶性心包积液

背景与目的:心包穿刺抽液后心包腔内药物治疗是治疗恶性心包积液的主要手段。本研究观察足叶乙甙(VP-16)联合顺铂(DDP)心包腔内注射治疗非小细胞肺癌恶性心包积液的疗效及不良反应。方法:对28例非小细胞肺癌恶性心包积液的患者行心包穿刺术,尽可能抽尽液体后心包腔内注入VP-16200～300mg和DDP80～100mg,局部治疗后2周行全身化疗。结果:28例患者首次治疗有效率85.7%,完全缓解率71.4%,2次治疗总有效率100%。仅4例患者需行二次穿刺治疗。治疗后胃肠道反应16例,主要为Ⅰ～Ⅱ度;骨髓抑制12例,主要为Ⅰ度;转氨酶轻度升高1例。24例初治患者中,ⅢB期患者中位生存期14个月,Ⅳ期患者中位生存期10.9个月;复发的4例患者中位生存期6个月(从复发日起计算)。结论:心包穿刺抽液加心包腔内注入VP-16联合DDP是恶性心包积液有效的治疗方法。