melphalan and Carcinoma--Non-Small-Cell-Lung

Mitomycin has proven to be among the most active drugs available for the single-agent treatment of non-small cell lung cancer (NSCLC). In combination with vinca alkaloids and cisplatin, mitomycin can produce response rates greater than or equal to 50% in properly selected patients. In our experience, such responses were achieved using moderate doses (7 or 8 mg/m2) of mitomycin, which also resulted in fewer hematologic and other toxicities. Delivery of MVP (mitomycin/vinca alkaloid/cisplatin) to 150 patients with stages III and IV NSCLC during the last decade showed maximal response was achieved after two or three cycles of therapy. A comparative analysis of results reported using MVP regimens suggests that high response rates are associated with greater dose-intensive use of cisplatin and lesser dose-intensive use of mitomycin. Although the role of MVP in the treatment of advanced NSCLC is unclear, use of mitomycin-containing regimens as part of a multidisciplinary approach to stage IIIA NSCLC has yielded high response rates and has successfully downstaged patients prior to surgery. Randomized clinical trials will be required to validate these findings, but the focus of future research should be on discovering new agents with greater activity and on developing new approaches wherein these agents can be delivered with maximum efficacy and minimum toxicity.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Combined Modality Therapy; Humans; Lung Neoplasms; Melphalan; Methotrexate; Mitomycin; Mitomycins; Progesterone; Vinblastine

The purpose of this study is to compare the efficacy and safety of Gefitinib versus VMP in combination with three-dimensional conformal radiotherapy (3D-CRT) for multiple brain metastases from non-small cell lung cancer (NSCLC). A total of 73 NSCLC patients with brain metastases from January 2010 to August 2013 were randomly divided into Gefitinib group (37 patients) and VMP chemotherapy group (36 patients). Patients in VMP group received VM-26 100 mg/day by intravenous injection, from day 1 to day 3, cisplatin 25 mg/m2 by intravenous injection, from day 1 to day 3. One cycle was defined as a 21-day therapy duration, with a total of 3 cycles; 2 cycles were used for consolidation. Patients in Gefitinib group received Gefitinib orally. Both groups received 3D-CRT, DT50 Gy/25f/35d from first day and target areas were treated with whole brain radiotherapy. The results of the study are listed below: There was no significant difference in the short-term effects of the two groups (P > 0.05). Median survival time (MST) of Gefitinib was 13.3 months whereas median survival time of VMP group is 12.7 months (P < 0.05). In Gefitinib group, we did not observe any difference of the median survival time between the patients with and without mutation EGFR. Toxicity of Gefitinib groups were characterized by rash, whereas chemotherapy resulted in hematologic toxicities, which included 6 cases of III/IV leucopenia (17.6 %), 3 cases of anemia (8.8 %), and 5 cases of thrombocytopenia (14.7 %), and non-hematological toxicity which was less serious symptoms for gastrointestinal disorders, hair loss, etc. These adverse reactions can be released after symptomatic treatment. No treatment-related deaths occurred. Two patients in VMP group quit due to IV leucopenia. Both oral Gefitinib and systemic VMP chemotherapy in combination with three-dimensional conformal radiotherapy (3D-CRT) could be used to treat brain metastases from non-small cell lung cancer. There were no difference in the short-term effects of the two groups, but long-term effect of Gefitinib group was slightly better than VMP group. Moreover, Gefitinib group showed low toxicity. All together, our finding implicated that Gefitinib is an effective method for patients with brain metastases from NSCLC.

Topics: Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Female; Gefitinib; Humans; Male; Melphalan; Middle Aged; Prednisolone; Quinazolines; Radiotherapy, Intensity-Modulated; Treatment Outcome; Vindesine

One hundred patients with non-small cell lung cancer were entered by members of the Northern California Oncology Group into a randomized Phase II trial of i.v. melphalan versus i.v. melphalan with concomitant oral misonidazole. The patients had not received prior chemotherapy. Eighty-five patients were evaluable for assessment of response and 89 were evaluable for toxicity analysis. The melphalan/misonidazole group had a superior response rate (two complete and four partial responses among 42 patients or 14%) compared to the melphalan group in which there were no responses among 43 patients (p = 0.024, two-sided Fisher exact test). Since hematological toxicity was equivalent in the two groups, there was an improvement in therapeutic index. Data from 12 patients undergoing pharmacological studies demonstrated that the plasma concentration of melphalan was 25% higher in the misonidazole group, a difference that is not statistically significant. Although the mechanism of interaction has not been fully established, this randomized trial demonstrates that a chemosensitizer can enhance the clinical antitumor activity of an alkylating agent and suggests that chemosensitizers in combination with alkylating agents should be investigated in further clinical trials.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Drug Evaluation; Female; Humans; Lung Neoplasms; Male; Melphalan; Middle Aged; Misonidazole

Fifteen patients with Stage IV lung cancer both untreated and previously treated were enrolled into a high-dose chemotherapy program with multiple alkylating agents and autologous bone marrow reinfusion. Eight patients received cyclophosphamide at 7.5 gm/m2 over 3 days with thiotepa escalated from levels of 1.8 mg/kg to 6.0 mg/kg over 3 days. Seven patients received the above dose of cyclophosphamide plus thiotepa at 675 mg/m2 and oral melphalan escalated from levels of 0.75 mg/kg to 2.5 mg/kg over 3 days. Both regimens are part of larger Phase I-II clinical studies. The median time to recovery of more than 500 granulocytes and more than 50,000 platelets per microliter was 16 and 27 days, respectively. Two patients died as a consequence of severe, overwhelming infections during their period of aplasia. Of the 13 evaluable patients, no patients achieved a complete response and seven patients (47%) obtained a partial response. The median duration of response was 12 weeks. Other nonhematologic toxicities included nausea/vomiting, diarrhea, mucositis, skin rash, hemorrhagic cystitis, and cardiomyopathy. Since there are substantial toxicities associated with high-dose chemotherapy and responses of such brief duration, further investigation with these drug combinations is not warranted.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carcinoma, Non-Small-Cell Lung; Combined Modality Therapy; Cyclophosphamide; Female; Humans; Lung Neoplasms; Male; Melphalan; Middle Aged; Neoplasm Staging; Thiotepa