Guadagni Stefano, Clementi Marco, Valenti Marco, Fiorentini Gianmaria, Cantore Maurizio, Kanavos Evangelos, Amicucci Gianfranco
Department of Surgical Sciences, University of L'Aquila, Italy.
In Vivo. 2006 Nov-Dec;20(6A):715-8.
Malignant pleural mesothelioma (MPM) is an aggressive treatment-resistant tumor with a median survival from diagnosis of 12 months. Although multimodality protocols that combine aggressive surgery and adjuvant chemotherapy or radiotherapy have shown improved survival in selected cases, the majority of patients with MPM are not suitable for radical surgery due to advanced stage and comorbid medical illness. For these patients combination chemotherapy with Pemetrex and Cisplatin should be considered for first line palliative chemotherapy. The therapeutic options available to patients with MPM resistant or refractory to systemic chemotherapy are very limited. Thoracic "stop-flow" perfusion (TSP) is a semi-invasive loco-regional drug delivery system that, limiting the circulation to the thorax during the anticancer agent's infusion, claims the advantage of reaching high drug concentration at the tumor site while maintaining a low systemic toxicity. The aim of this phase I-II study was to evaluate the toxicity profile and efficacy of two different platinum-based combined regimens--cisplatin plus mitomycin-C (MMC) and cisplatin plus melphalan (L-PAM)--administered using TSP technique in patients with advanced or recurrent MPM who had refractory disease after systemic first line chemotherapy. Patients with histologically proven unresectable stage II-III MPM entered this trial. Between January 1995 and December 2001, 27 patients were enrolled in the study and submitted to TSP using the two different chemotherapy cisplatin based regimens: 12 patients received cisplatin 100 mg/m2 plus MMC 20 mg/m2 (MMC arm) and 15 cisplatin 100 mg/m2 plus L-PAM 50 mg/m2 (L-PAM arm). Objective responses were assessed by CT-scan 30 and 60 days after the end of treatment in all 27 enrolled patients. Two patients (7.4%) achieved a complete response, 2 (7.4%) a partial response and 4 (14.8%) a minor response. The remaining 19 patients (70.3%) showed a stable disease. No patients developed progression of the disease following the first TSP. The overall median time to progression was 8.9 months (range 1-41). The median survival time for all patients from the beginning of regional chemotherapy was 16.6 months, with a 1-year survival rate of 62.9%, a 2-year survival rate of 18.5%, and a 3-year survival rate of 7.4%. Our data show that TSP is a relatively effective second-line treatment in patients with progressive disease after systemic chemotherapy, with a low rate of major complications and treatment-related toxicity.
恶性胸膜间皮瘤（MPM）是一种侵袭性强且对治疗耐药的肿瘤，确诊后的中位生存期为12个月。尽管将积极手术与辅助化疗或放疗相结合的多模式方案在部分病例中显示出生存期改善，但大多数MPM患者由于疾病晚期和合并内科疾病而不适合进行根治性手术。对于这些患者，应考虑使用培美曲塞和顺铂联合化疗作为一线姑息化疗方案。对于对全身化疗耐药或难治的MPM患者，可用的治疗选择非常有限。胸部“停流”灌注（TSP）是一种半侵入性局部区域给药系统，在抗癌药物输注期间限制药物循环至胸部，声称具有在肿瘤部位达到高药物浓度同时保持低全身毒性的优势。这项I-II期研究的目的是评估在一线全身化疗后疾病难治的晚期或复发性MPM患者中，使用TSP技术给予两种不同的铂类联合方案——顺铂加丝裂霉素-C（MMC）和顺铂加美法仑（L-PAM）——的毒性特征和疗效。组织学证实为不可切除的II-III期MPM患者进入该试验。1995年1月至2001年12月，27例患者入组该研究并使用两种不同的基于顺铂的化疗方案接受TSP：12例患者接受顺铂100mg/m²加MMC 20mg/m²（MMC组），15例接受顺铂100mg/m²加L-PAM 50mg/m²（L-PAM组）。在所有27例入组患者治疗结束后30天和60天通过CT扫描评估客观缓解情况。2例患者（7.4%）达到完全缓解，2例（7.4%）部分缓解，4例（14.8%）轻微缓解。其余19例患者（70.3%）疾病稳定。首次TSP后无患者疾病进展。从区域化疗开始所有患者的总中位进展时间为8.9个月（范围1-41个月）。所有患者从区域化疗开始的中位生存时间为16.6个月，1年生存率为62.9%，2年生存率为18.5%，3年生存率为7.4%。我们的数据表明，TSP是全身化疗后疾病进展患者相对有效的二线治疗方法，主要并发症和治疗相关毒性发生率低。
