Vinblastine Mitomycin

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

Hemolysis, as a result of the development of antielliptinium antibodies, was observed in 5 patients, and 1 patient had cumulative renal toxicity. Another study of advanced breast cancer in previously treated patients showed 1 complete remission, 4 partial remissions, and 6 minor responses of 33 evaluable patients 281). The authors concluded that elliptinium has modest but unmistakable activity and needs to be evaluated further in combination with other drugs. Indeed, one such study in which 5 was used in combination with mitomycin, vinblastine, and/or etoposide indicates that this mix of agents was active and well tolerated in patients with advanced breast cancer (282). 

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). 

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. 

Drugs have included N-mustards, doxorubicin, taxol, mitomycin, vinblastine, etc. 

Ozols RF, Hogan WM, Ostchega T, Young RC. MVP (mitomycin, vinblastine, progesterone) a second-line regimen in ovarian cancer with a hi incidence of pulmonary toxicity. Cancer Treat Rep ( 9Zy) 67,721-2. 

MVP mitomycin C/ vinblastine/ Mitomycin C 8 mg/M2 IV day 1 (of every other course)... 

Other examples of natural drugs may be pointed out streptozotocin (from streptomyces achromogenes), bleomycin (from streptomyces verticillus), adriamy-cin and daunomycin (from streptomyces pencetius), mitomycin C (from streptomyces caesipitosus), vincristine, vinblastine and vindoline (from catharanthus roseus or vinca rosea L.). 

Combination studies with PKCa antisense and standard chemotherapeutic agents (cis-platin, mitomycin-C, vinblastine, estracyt and adriamycin) in nude mice that had been transplanted with a variety of human tumors (breast, prostate, large cell lung and small cell lung carcinomas, and melanomas) were found to be additive or superadditive (Geiger et al, 1998). 

B = bleomycin, C = chlorambucil, CT = chemotherapy, DFS = disease-free survival, Ep = epirubicin, F = fluorouracil, I = ifosfamide, M = mitomycin C, Mtx = methotrexate, O = vincristine, OS = overall survival, P = cisplatin, RT = radiation therapy, V = vinblastine. 

Another area in which natural products have had a major impact on longevity and quality of life is in the chemotherapy of cancer (see Chapter 62). In fact, most major anticancer drugs are derived from plants or microorganisms. Important examples include bleomycin, doxorubicin, daunorubicin, vincristine, vinblastine, mitomycin, streptozocin, and most recently, paclitaxel... 

Carcinoma of lung Cisplatin plus taxane Methotrexate, vincristine, vinblastine, doxorubicin, mitomycin C... 

Using PEGylated liposomal doxorubicin (Caelyx), Keller et al. [427] compared the efficacy of the liposomal formulation with that of a common regimen in patients with taxane-refractory advanced breast cancer. The regimen scheme was Caelyx (50 mg/m2 every 28 weeks) or vinorelbine (30 mg/m2) or mitomycin C (10 mg/m2 every 28 days) plus vinblastine (5mg/m2 at days 1,14, 28, 42). Finally, progression free survival and overall survival were similar for Caelyx and the comparative regimen. 

Keller, A. M., Mennel, R. G., Georgoulias, V. A., Nabholtz, J. M., Erazo, A., Lluch, A., Vogel, C. L., Kaufmann, M., Minckwitz, G., Henderson, G., Mellars, L., Alland, L., and Tendler, G. (2004), Randomized phase III trial of pegylated liposomal doxorubicin versus vinorelbine or mitomycin C plus vinblastine in women with taxane-refractory advanced breast cancer./. Clin. Oncol., 22, 3893-3901. 

VINBLASTINE MITOMYCIN-C t risk of abrupt onset of pulmonary toxicity in 3-6% of patients, when two courses of these drugs are administered concurrently Mechanism is uncertain possible additive pulmonary toxic effects Monitor clinically and with lung function tests for pulmonaiy toxicity. Advise patients to report immediately symptoms such as shortness of breath and wheezing... 

Actinomycin D, bisantrene, chlorambncil, cisplatin, cytarabine, dannornbicin, docetaxel, doxorubicin, epirn-bicin, etoposide, flnoro uracil, hydroxyurea, mitomycin C, mitoxantrone, paclitaxel, tamoxifen, topotecan, taxol, vinblastine, vincristine. 

Lung non-small cell) MIC mitomycin + ifosfamide cisplatin MVPi micomycin + vinblastine + cisplatin Cisplatin + gemcitabine vinorelbine... 

Acute shortness of breath and bronchospasm have been reported after the administration of vinca alkaloids, for example vinblastine and vindesine (30-34). The respiratory effects, including abrupt onset of progressive dyspnea, non-productive cough, pleuritic chest pain, profound wheezing, and diffuse basal crackles, were more common when mitomycin was used concomitantly. The onset of symptoms can be rapid (for... 

Prestifilippo J, Lewin D. Dyspnea following vinblastine or vindesine administration in patients receiving mitomycin plus vinca alkaloid combination therapy. Cancer Treat Rep 1984 68(7-8) 1029-31. 

Ballen KK, Weiss ST. Fatal acute respiratory failure following vinblastine and mitomycin administration for breast cancer. Am J Med Sci 1988 295(6) 558-60. 

Hoelzer KL, Harrison BR, Luedke SW, Luedke DW. Vinblastine-associated pulmonary toxicity in patients receiving combination therapy with mitomycin and cisplatin. Drug Intell Clin Pharm 1986 20(4) 287-9. 

Camptothecin analogs Irinotecan Topotecan Epipodophyllotoxins Etoposide Teniposide Antitumor antibiotics Bleomycin Dactinomycin Daunorubicin Doxorubicin Epirubicin Idarubicin Mitomycin Mitoxantrone Valrubicin Microtubule agents Docetaxel Paclitaxel Vinblastine Vincristine Vinorelbine Enzymes Asparaginase Pegasparaginase Metals... 

Vinblastine and vindesine can increase the pulmonary toxicity of mitomycin C. Severe and life-threatening bronchospasms and two cases of fatal acute respiratory failure have been reported. 

Clinically important, potentially hazardous interactions with altretamine, amikacin, aminoglycosides, antineoplastics, bleomycin, busulfan, carboplatin, carmustine, chlorambucil, cisplatin, corticosteroids, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin, docetaxel, doxorubicin, estramustine, etoposide, fludarabine, fluorouracil, gemcitabine, gentamicin, hydroxyurea, idarubicin, ifosfamide, indomethacin, kanamycin, levamisole, lomustine, mechlorethamine, melphalan, mercaptopurine, methotrexate, mitomycin, mitotane, mitoxantrone, neomycin, pentostatin, plicamycin, procarbazine, streptomycin, streptozocin, thioguanine, thiotepa, tobramycin, tretinoin, uracil, vinblastine, vincristine, vinorelbine... 

Keller AM et al (2004) Randomized phase III trial of pegylated liposomal doxorubicin versus vinorelbine or mitomycin C plus vinblastine in women with taxane-reftactory advanced breast cancer. J CUn Oncol 22 3893-3901... 

Biedler and coworkers [123] reported that Chinese hamster cells selected for resistance to actinomycin D also showed cross-resistance to mithramycin, vinblastine, vincristine, puromycin, dauromycin, democolcine, and mitomycin C. Thus, upon selection with a single cytotoxic drug, mammalian cells became simultaneously cross-resistant to a range of drugs with different chemical structures and molecular... 

Rarely, azathioprine and its major metabohte 6-mercaptopurine have been reported to produce an acute restrictive lung disease. Procarbazine, a methylhydrazine associated more commonly with Loef-fler s syndrome, rarely has been associated with pulmonary fibrosis. The vinca alkaloids vinblastine and vindesine have been reported to produce severe respiratory toxicity in association with mitomycin. The incidence with the combination is 39% and may represent a true synergistic effect between these agents. ... 

The combination of vinblastine and mitomycin C has caused shortness of breath and bronchospasm. Vinblastine reduces the level and, hence, the effectiveness of phenytoin, requiring increased dosage. Vinblastine produces nausea and vomiting and marrow depression as well as alopecia (see Figure 15). 

Among all ABC transporters, P-gp, also known as MDRl protein, ABCBl or CD243, is probably the most studied and characterized member. It was first found as a 170-kDa ATP-dependent membrane glycoprotein that acts as a drug efflux pump [15], P-gp is a broad-spectrum transporter, capable of transporting several structurally and functionally unrelated substrate molecules. Its substrates are typically hydrophobic, amphipathic products, including many chemotherapeutic compounds used for cancer treatment, e.g., vinca alkaloids (vincristine, vinblastine), taxanes (paclitaxel, docetaxel), epipodophyllotoxins (etoposide, teniposide), anthracyclines (doxorubicin, daunorubicin, epirubicin), topotecan, dactinomycin, and mitomycin-C [37]. 

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