Thoracic stop-flow perfusion for refractory lymphoma: a phase I-II evaluation trial.

BACKGROUND: Management of patients with heavily pretreated malignant lymphoma failing front-line treatment and salvage high-dose chemotherapy and autologous peripheral stem cell rescue is problematic. A phase I-II evaluation trial was conducted to evaluate thoracic stop-flow perfusion. PATIENTS AND METHODS: nine refractory patients were enrolled in the study. The schedule of thoracic stop-flow perfusion was based on cisplatin (100 mg/m(2)) and melphalan (25 mg/m(2)). Melphalan pharmacokinetic analyses were performed. All patients received hemofiltration during each procedure. RESULTS: Overall 18 cycles of perfusional chemotherapy were administered. During the procedures there were no technical, hemodynamic, or vascular complications, and no deaths occurred during surgery. Hematological and non-hematological toxicity was mild in relation to the use of hemofiltration during the procedures. All 9 patients responded favourably to stop-flow therapy. We observed 5 CR and 4 PR. Four out of five patients in CR relapsed. Three out of these four died of progressive disease after a response duration of 9, 7 and 7 months, respectively. One patient had a duration of CR of 10 months before relapse. He attained a new PR (+ 3 months). The remaining complete responder is still in remission after 37+ months. The 4 patients in PR progressed and died after a response duration of 4, 6, 2 and 1 month, respectively. To date, 8 out of 9 patients have died and one is still alive. CONCLUSION: Thoracic stop-flow perfusion seems very active in this kind of patient.

Selected hypoxic stop-flow perfusions: indication and limits.

AIMS AND BACKGROUND: The treatment of unresectable cancers is still one of the main medical challenges. Stop-flow perfusion has been used as locoregional chemotherapy based on blood supply blockage of the tumor-bearing area. The aim of the present paper is to report our personal experience in the clinical use of hypoxic stop-flow perfusion and discuss future prospects for research. METHODS AND STUDY DESIGN: Since December 1997 more than 500 stop-flow perfusions have been performed at the University of L'Aquila. Hypoxic perfusion was adopted for the following indications: recurrent rectal cancer, advanced pancreatic cancer, recurrent pelvic and limb melanoma, and recurrent limb melanoma. RESULTS: For recurrent rectal cancer median survival was 12.2 months, for advanced pancreatic cancer 9.6 months, for recurrent pelvic and limb melanoma 34.4 months, and for recurrent limb melanoma 23.8 months. CONCLUSIONS: Based on these encouraging results, stop-flow perfusion should be considered an effective treatment. Future fields of research include tailored chemotherapy and hyperthermia.

Thoracic stop-flow perfusion in the treatment of refractory malignant pleural mesothelioma: a phase I-II evaluation/trial.

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.