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)

Epirubicin is the 4' epimer of the anthracycline antibiotic doxorubicin, and has been used alone or in combination with other cytotoxic agents in the treatment of a variety of malignancies. Comparative and noncomparative clinical trials have demonstrated that regimens containing conventional doses of epirubicin achieved equivalent objective response rates and overall median survival as similar doxorubicin-containing regimens in the treatment of advanced and early breast cancer, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), non-Hodgkin's lymphoma, ovarian cancer, gastric cancer and nonresectable primary hepatocellular carcinoma. Recently, dose-intensive regimens of epirubicin have achieved high response rates in a number of malignancies including early and advanced breast cancer and lung cancer. The major acute dose-limiting toxicity of anthracyclines is myelosuppression. In vitro and clinical studies have shown that, at equimolar doses, epirubicin is less myelotoxic than doxorubicin. The lower haematological toxicity of epirubicin, as well as the recent introduction of supportive measures such as colony-stimulating factors, has allowed dose-intensification of epirubicin-containing regimens, which is particularly significant because of the definite dose-response relationship of anthracyclines. Cardiotoxicity, which is manifested clinically as irreversible congestive heart failure and/or cardiomyopathy, is the most important chronic cumulative dose-limiting toxicity of anthracyclines. Epirubicin has a lower propensity to produce cardiotoxic effects than doxorubicin, and its recommended maximum cumulative dose is almost double that of doxorubicin, thus allowing for more treatment cycles and/or higher doses of epirubicin. In summary, dose-intensive epirubicin-containing regimens, which are feasible due to its lower myelosuppression and cardiotoxicity, have produced high response rates in early breast cancer, a potentially curable malignancy, as well as advanced breast, and lung cancers. Furthermore, there is evidence to suggest that improved response rates can improve quality of life in some clinical settings, but whether this leads to prolonged survival has not yet been determined. Recently implemented supportive measures such as colony-stimulating factors, prophylactic antimicrobials and peripheral blood stem cell support may help achieve other potential advantages of dose-intensive epirubicin-containing regimens such as reductions in morbidity and length of hospital admissions.

Epirubicin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in cancer chemotherapy.

37 Hochster H (1994) A multicenter Phase II study of navelbine (NVB) and doxorubicin (DOX) as first line chemotherapy of metastatic breast cancer. Pr Annu Meet Am Soc Clin Oncol 13: Abstract 203 Jehl F, Quoix E, Leveque D, Pauli G, Breillout F, Krikorian A and Monteil H (1991 Pharmacokinetics and preliminary metabolic fate of navelbine in humans as determined by high performance liquid chromatography. Cancer Res47:

/pdf/vinorelbine-a-clinical-review-593uzh0v51.pdf

Vinorelbine – a clinical review

https://www.jto.org/article/S1556-0864(15)30874-1/pdf

Third-Generation Chemotherapy Agents in the Treatment of Advanced Non-small Cell Lung Cancer: A Meta-Analysis

The frequency, risk factors, pathophysiology, diagnosis, and management of lung cancer are reviewed. An estimated 157,400 Americans died of lung cancer in 2001. Lung cancer is the second most frequent cancer in both men and women. The major risk factor for lung cancer is smoking, which accounts for 75-80% of lung cancer-related deaths. Lung cancers can be broadly classified into two forms, small-cell carcinomas and non-small-cell carcinomas. Non-small-cell lung cancer is more common, accounting for up to 75% of lung cancers. Lung cancer is diagnosed by chest radiography, sputum cytology, bronchoscopy, needle biopsy, and other techniques. Surgery plays a major role in managing stage I and stage II non-small-cell lung cancer and may be used for stage III disease. Patients with stage IIIa disease may be surgical candidates, but involvement of mediastinal lymph nodes reduces the probability of survival. Adjuvant irradiation may reduce the rate of local recurrence but does not increase survival time. Adjuvant chemotherapy may confer a small survival-time advantage if the regimen includes cisplatin. Chemotherapy combined with radiation therapy may produce a survival advantage over irradiation alone. Patients with advanced non-small-cell lung cancer should receive combination chemotherapy. Several regimens have shown a survival advantage over best supportive care. Paclitaxel, docetaxel, gemcitabine, vinorelbine, irinotecan, and topotecan have activity both as single agents and in combination. Surgery has only a limited role in the management of small-cell lung cancer. Patients with limited disease should receive a platinum-based chemotherapy regimen plus radiation therapy. Combination chemotherapy should be offered to patients with extensive disease. The most active regimens contain cisplatin or carboplatin. Paclitaxel, docetaxel, gemcitabine, vinorelbine, irinotecan, and topotecan combinations have shown some promise. Lung cancer, although highly preventable, is usually diagnosed at an incurable stage. Chemotherapy is playing an increasingly important role alongside surgery and radiation therapy in the management of this disease.

Lung cancer: a review

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

Preventive epoetin a (EPO) use in the treatment of advanced nsclc: an AIPO oncology study group multicenter trial

[MACC plus thymostimulin (TP-1 Serono) therapy of small cell bronchogenic carcinoma. Clinico-immunologic evaluation of the results of a randomized trial].

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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

Preventive epoetin a (EPO) use in the treatment of advanced nsclc: an AIPO oncology study group multicenter trial

[MACC plus thymostimulin (TP-1 Serono) therapy of small cell bronchogenic carcinoma. Clinico-immunologic evaluation of the results of a randomized trial].