Mitomycin lung cancer

Mitomycin C Lung cancer. Various disseminated refractory malignandes. Gastric cancer... 

CALGB, Cancer and Leukemia Group B LCSG, Lung Cancer Study Group MVP, mitomycin/ vinblastine/cisplatin VP, vinblastine/cisplatin RT, radiation therapy. 

Furuse K, Fukuoka M, Kawahara M, et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III nonsmall cell lung cancer. J Clin Oncol 1999 17 2692-2699. 

Various new benzimidazole-4,1-diones (xv) substituted at 2-position were synthesized via a microwave assisted reaction by Gellis et al. [24], Their cytotoxicity has been evaluated on the colon, breast and lung cancer cell lines and good results were observed comparable to that of mitomycin C. 

Forty patients with lung cancer, treated with a combination of cisplatin, mitomycin, vinblastine, doxorubicin, cyclosphosphamide, and methotrexate, had a significant post-treatment increase in fibrinopeptide A and a fall in fibrinolytic activity, reflected by a fall in functional tissue activator this appeared to be cumulative, depending on the extent of drug exposure (184). 

Cartel G, Cartel F, Cantone A, et al. Cisplatin-cyclophosphamide-mitomycin combination chemotherapy with supportive care versus supportive care alone for treatment of metastatic nonsmall-cell lung cancer. J Natl Cancer Inst 1993 85 794-800. 

Smith IE, O Brien ME, Talbot DC, et al. Duration of the chemotherapy in advanced non-small-cell lung cancer A randomized trial of three versus six courses of mitomycin, vinblastine, and cisplatin. J Clin Oncol 2001 19 1336-1343. 

The in vitro phase II trial of RA-700 employed human tumor clonogenic assay. From the results using a human tumor cell line of lung cancer (PC-6), RA-700 appears to possess time-dependent antitumor activity. The chemosensitivity rate of RA-700 was 67%, 22%, 17% and 10% for ovarian cancer, non-small cell lung cancer, breast cancer and colorectal cancer, respectively. RA-700 showed almost the same chemosensitivity as that of five standard anticancer drugs (adryamycin, mitomycin C, cisplatin, vinbrastine and 5-FU), but the spectrum of RA-700 activity appeared to be different. Furthermore, the antitumor activity of RA-700 had no relationship with prior chemotherapy. These results indicated that RA-700 is a candidate for phase I study [89]. 

Von Rohr, A., Anderson, A., McIntosh, R., and Thatcher, N. (1991). Phase II study with mitomycin, ifosfamide and carboplatin in inoperable non-small cell lung cancer. Eur. J. Cancer 9,1106-1108. 

Streptomyces caespitosus produces several mitomycins, antibiotics that show an excellent antitumor activity but of limited utility because of their toxicity. The only substance acceptable for human use is mitomycin C, approved by FDA in 1974. Mitomycin C acts by forming covalent bridges across two opposite DNA strands, causing a rapid cell death (Tomasz 1995). In contrast to most antitumor agents, it is also active against the hypoxic cells in the core of solid tumors and therefore is indicated for the treatment of specific type of neoplasms such as gastric, colorectal, and lung cancer. 

Short term treatment with TPA sensitized human 2008 ovarian carcinoma cells to cis-platin. This sensitization disappeared completely by seven hours after treatment, indicating that not inhibition, but activation of PKC sensitizes 2008 cells to the antiproliferative activity of cis-platin (Isonishi et al., 1990). Pretreatment of HeLa cells with TPA or PdBu caused a 9-fold increase in cellular sensitivity to cis-platin and 2.5-fold to melphalan, but had now effect on the antiproliferative activity of bleomycin, adriamycin, vincristine, or mitomycin C. The sensitization of HeLa cells by TPA was associated with a 6-fold stimulation of PKC activation and a concentration- and time-dependent increase in cellular platinum content. (Basu et al. 1990). PKC activity was found to be decreased significantly in cis-platin-resistant human small cell lung H69/CP cancer cells compared to the drug-sensitive variant. A similar reduction in PKC activity was noted in ovarian carcinoma 2008 cells that were resistant to cis-platin. A modest decrease in PKC activity was also observed in etoposide-resistant H69 cells but not in taxol-resistant H69 cells or bleomycin-resistant human head and neck carcinoma A-253 cells (Basu et al., 1996), indicating that reduced PKC activity leads to decreased sensitivity in this system. 

Mitomycin C is used as an antineoplastic agent and for slowing of fibroblast formation in open-angle glaucoma. Recently, mitomycin C has been used to induce tumor responses in patients with many types of cancer. For example, mitomycin C is used in the palliative treatment of various solid tumors such as nonsmall cell lung, cervical, colorectal, breast, bladder, pancreatic, and esophageal carcinomas. In addition to... 

---