http://europepmc.org/articles/PMC4146684?pdf=render

Cisplatin in cancer therapy: molecular mechanisms of action

Cisplatin: The first metal based anticancer drug.

Malignant pleural mesothelioma (MPM) is a deadly disease that occurs in 2,000 to 3,000 people each year in the United States. Although MPM is an extremely difficult disease to treat, with the median overall survival ranging between 9 and 17 months regardless of stage, there has been significant progress over the last few years that has reshaped the clinical landscape. This article will provide a comprehensive discussion of the latest developments in the treatment of MPM. We will provide an update of the major clinical trials that impact mesothelioma treatment in the resectable and unresectable settings, discuss the impact of novel therapeutics, and provide perspective on where the clinical research in mesothelioma is moving. In addition, there are controversial issues, such as the role of extrapleural pneumonectomy, adjuvant radiotherapy, and use of intensity-modulated radiotherapy versus hemithoracic therapy that will also be addressed in this manuscript.

/pdf/malignant-pleural-mesothelioma-3q3fseypjk.pdf

Malignant pleural mesothelioma

Radical surgery is the standard of care for fit stage I non-small cell lung cancer (NSCLC) patients. Adjuvant treatment should be offered only as part of an investigation trial. Stage II and IIIA adjuvant cisplatin-based chemotherapy remains the gold standard for completely resected NSCLC tumors. Additionally radiotherapy should be offered in patients with N2 lymph nodes. In advanced stage IIIB/IV or inoperable NSCLC pts, a multidisciplinary treatment should be offered consisted of 4 cycles of cisplatin-based chemotherapy plus a 3 rd generation cytotoxic agent or a cytostatic (anti-EGFR, anti-VEGFR) drug.

/pdf/treatment-of-non-small-cell-lung-cancer-nsclc-2r7ayi3ou3.pdf

Treatment of non-small cell lung cancer (NSCLC)

PURPOSEWe studied a multimodality approach using extrapleural pneumonectomy, chemotherapy, and radiotherapy in patients with malignant pleural mesothelioma.PATIENTS AND METHODSFrom 1980 to 1992, 52 selected patients, underwent treatment. Median age was 53 years (range, 33 to 69). Initial patient evaluation was performed by a multimodality team. Pathologic diagnosis was reviewed and confirmed before therapy. Patients with no medical contraindication and potentially resectable mesothelioma on computed tomography (CT) (magnetic resonance imaging [MRI] when it became available) received extrapleural pneumonectomy, cyclophosphamide, doxorubicin, and cisplatin (CAP) chemotherapy, and radiotherapy.RESULTSPerioperative morbidity and mortality rates were 17% and 5.8%, respectively. The overall median survival duration is 16 months (range, 1 month to 8 years). The 32 patients with epithelial histologic variant had 1-, 2-, and 3-year survival rates of 77%, 50%, and 42%, respectively. Patients with mixed and sarcomat...

Node status has prognostic significance in the multimodality therapy of diffuse, malignant mesothelioma

In the present multicentre randomized phase II trial, the activity and toxicity of three platinum-based combination regimens for the treatment of advanced non-small-cell lung cancer (NSCLC) were evaluated. The three regimens were: MVP (mitomycin-C 6 mg m(-2) on day 1, vindesine 3 mg m(-2) on days 1 and 15, and cisplatin 80 mg m(-2) on day 1 every 28 days), PIN (cisplatin 80 mg m(-2) day 1, ifosfamide 3 g m(-2) day 1 and vinorelbine 25 mg m(-2) day 1 and 8 every 21 days) and CaN (carboplatin 350 mg m(-2) day 1 and vinorelbine 25 mg m(-2) days 1 and 8 every 28 days). A total of 140 chemotherapy-naive patients entered the study; 49 patients were treated with MVP, 48 with PIN and 43 with CaN. Sixty-seven per cent of the patients had stage IV disease. Response rates, calculated on an 'intention to treat' basis, were as follows: MVP, 14.3% (95% CI 5.94-27.2%); PIN, 16.7% (95% CI 7.4-30.2%); and CaN, 14% (95% CI 5.3-27.9%). The overall median survivals were 256, 269 and 243 days for patients treated with MVP, PIN and CaN respectively. Myelosuppression was the most frequent toxicity: grade 3-4 leucopenia was observed in 14.3%, 25% and 18.6% of patients treated with MVP, PIN and CaN respectively. This multicentre phase II randomized trial shows that MVP, PIN and CaN can be administered on an outpatient basis with acceptable toxicities. Unfortunately, the three regimens showed an activity significantly lower than that reported in previous single-institution phase II trials.

Cisplatin-vindesine-mitomycin (MVP) vs cisplatin-ifosfamide-vinorelbine (PIN) vs carboplatin-vinorelbine (CaN) in patients with advanced non-small-cell lung cancer (NSCLC): a FONICAP randomized phase II study. Italian Lung Cancer Task Force (FONICAP).

Thirty-four patients with previously untreated advanced non-small-cell lung cancer were treated with a combination of polychemotherapy and recombinant interferon. Chemotherapy consisted of cyclophosphamide, 400 mg/m2, epidoxorubicin, 50 mg/m2, and cisplatin, 40 mg/m2 (CAP) i.v. on day 4; recombinant alpha 2b interferon (r alpha 2b IFN) was given i.m. daily at the dose of 3-5 MU from days 1 to 7. The treatment was repeated every 4 weeks. In the 32 eligible patients the overall response rate was 19.3% (95% C.L. 7.4-37.4%). Non-hematologic toxicity consisted formerly in flulike symptoms and fatigue complained of by 37.5% and 31.2% of patients, respectively, and vomiting reported in 68.7% of patients; grade III-IV myelotoxicity was observed in 12.5% of cases. In no case was the toxicity life threatening. The median overall actuarial survival and progression-free survival were 37 and 20 weeks, respectively. This study indicates that the combination of CAP chemotherapy and r alpha IFN is feasible and active in the treatment of advanced non-small-cell lung cancer.

Combination Chemotherapy and Interferon α2b in the Treatment of Advanced Non-Small-Cell Lung Cancer

Twenty-six symptomatic patients with diffuse malignant pleural mesothelioma (DMPM) were enrolled in a Phase II Italian Lung Cancer Task Force (FONICAP) study to assess the activity and toxicity of doxorubicin and cisplatin combination chemotherapy. The drug schedule was as follows; 60 mg/m2 of doxorubicin and 60 mg/m2 of cisplatin both given intravenously (IV) on day 1 every 3 to 4 weeks. Of the 24 evaluable patients, 6 objective partial responses (25%; 95% confidence limits, 9.77% to 46.71%) were observed. Twelve of 24 patients (50%), including 6 with no radiologic evidence of response, had a clinical improvement as demonstrated by an objective reduction of symptom or performance status scores along treatment. The overall median survival time was 10 months. Toxicity was mild and dose reductions or suspensions were not required. The combination of doxorubicin and cisplatin is effective and well tolerated. It might be considered for palliation of symptomatic patients with DMPM.

Activity of doxorubicin and cisplatin combination chemotherapy in patients with diffuse malignant pleural mesothelioma. An italian lung cancer task force (FONICAP) phase II study

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Cisplatin-vindesine-mitomycin (MVP) vs cisplatin-ifosfamide-vinorelbine (PIN) vs carboplatin-vinorelbine (CaN) in patients with advanced non-small-cell lung cancer (NSCLC): a FONICAP randomized phase II study. Italian Lung Cancer Task Force (FONICAP).

Combination Chemotherapy and Interferon α2b in the Treatment of Advanced Non-Small-Cell Lung Cancer

Activity of doxorubicin and cisplatin combination chemotherapy in patients with diffuse malignant pleural mesothelioma. An italian lung cancer task force (FONICAP) phase II study