A phase II pilot trial of concurrent biochemotherapy with cisplatin, vinblastine, dacarbazine, interleukin 2, and interferon alpha-2B in patients with metastatic melanoma.
A phase II pilot trial of concurrent biochemotherapy with cisplatin, vinblastine, dacarbazine, interleukin 2, and interferon alpha-2B in patients with metastatic melanoma.
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发表时间：
2000-06
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通讯作者：
David F. McDermott;J. Mier;Donald P. Lawrence;Marcel R.M. van den Brink;Marquerite A. Clancy;Krista M. Rubin;M. Atkins
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作者：
David F. McDermott;J. Mier;Donald P. Lawrence;Marcel R.M. van den Brink;Marquerite A. Clancy;Krista M. Rubin;M. Atkins
为了开发一种适合合作群体测试的转移性黑色素瘤的生物化疗方案，我们修改了s.s. Legha等人的同步生物化疗方案。肿瘤防治杂志。通过提供加强的支持性护理和制定严格、保守的方法来管理治疗相关的毒性。患者接受顺铂、长春碱和达卡巴嗪治疗（CVD：顺铂（20mg /m2）和长春碱（1.2 mg/m2）第1-4天，达卡巴嗪（800 mg/m2）第1天），同时持续静脉输注白细胞介素2 （9 MIU/m2/天）第1-4天，ifn - α （5 MU/m2/天）第1-5、8、10、12天。预防性抗生素和最多四个周期的管理。患者7和14分别开始常规粒细胞集落刺激因子和积极止吐药。44名患者参加了这项研究。没有患者之前接受过化疗或白细胞介素2；然而，23人（53%）先前接受过ifn - α治疗，主要是辅助治疗。总共进行了131个治疗周期。需要调整剂量的显著毒性包括：需要降压药的低血压（11例患者15次发作），3/4级呕吐(15个周期12次发作；12例患者5次发作（改良止吐方案开始后9个周期6次发作），短暂性肾功能不全（5例患者5次发作），4级血小板减少（24次发作，1次伴有出血），中性粒细胞减少伴或不伴发热（15例，常规使用粒细胞集落刺激因子后112个周期只有11例），导管相关菌血症（2例）。在最后一次方案修改后接受治疗的30名患者中，有5名（16%）经历了我们定义为合作组环境中不可接受的毒性。40例可评估患者中有19例出现缓解（相对风险，48%），8例完全缓解（20%）。中位反应持续时间为7个月（范围1-17+个月），其中1例正在进行中。11例有反应的患者复发部位为中枢神经系统。中位生存期为11个月（范围2-31个月）。这种改良的、同步的生物化疗方案在合作群体中使用是有效和耐受的。然而，中枢神经系统复发仍然是应答者关注的问题。该方案正在一项III期组间试验（东部合作肿瘤组/西南肿瘤组3695）中与CVD进行比较。
In an effort to develop a biochemotherapy regimen for metastatic melanoma suitable for testing in a cooperative group setting, we modified the concurrent biochemotherapy regimen of S. S. Legha et al. (J. Clin. Oncol., 16: 1752-1759, 1998) by providing enhanced supportive care and developing a strict, conservative approach to the management of treatment-related toxicities. Patients received cisplatin, vinblastine, and dacarbazine (CVD: cisplatin (20 mg/m2) and vinblastine (1.2 mg/m2) on days 1-4, dacarbazine (800 mg/m2) on day 1 only) concurrently with interleukin 2 (9 MIU/m2/day) by continuous i.v. infusion on days 1-4 and IFN-alpha (5 MU/m2/day) on days 1-5, 8, 10, and 12. Prophylactic antibiotics and a maximum of four cycles were administered. Routine granulocyte colony-stimulating factor and aggressive antiemetics were initiated after patients 7 and 14, respectively. Forty-four patients were enrolled in this study. No patients had received prior chemotherapy or interleukin 2; however, 23 (53%) had received prior IFN-alpha, mostly in the adjuvant setting. A total of 131 treatment cycles was administered. Significant toxicities requiring dose modification included: hypotension requiring pressors (15 episodes in 11 patients), grades 3/4 vomiting (12 episodes in 15 cycles; 5 episodes in 12 patients (6 episodes in 9 cycles after initiation of the modified antiemetic regimen), transient renal insufficiency (5 episodes in 5 patients), grade 4 thrombocytopenia (24 episodes, 1 associated with bleeding), neutropenia with or without fever (15 instances, only 11 in 112 cycles after routine use of granulocyte colony-stimulating factor), and catheter-related bacteremia (2 patients). Five (16%) of 30 patients who were treated after the last protocol modification experienced what we defined as unacceptable toxicity for a cooperative group setting. Responses were seen in 19 of 40 evaluable patients (relative risk, 48%) with 8 complete responses (20%). The median response duration was 7 months (range, 1-17+ months) with one currently ongoing. The central nervous system was the initial site of relapse in 11 responding patients. The median survival duration was 11 months (range, 2-31 months). This modified, concurrent biochemotherapy regimen is active and tolerable for use in a cooperative group setting. Central nervous system relapse, however, remains a concern for responders. This regimen is being compared with CVD in a Phase III Intergroup Trial (Eastern Cooperative Oncology Group/Southwest Oncology Group 3695).