Vinblastine lung cancer

VP Vinblastine/vindesine, cisplatinum Non-small cell lung cancer... 

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

Vinorelbine is a semisynthetic derivative of vinblastine whose mechanism of action is identical to that of vinblastine and vincristine, ie, inhibition of mitosis of cells in the M phase through inhibition of tubulin polymerization. This agent has activity in non-small cell lung cancer, breast cancer, and ovarian cancer. Myelosuppression with neutropenia is the dose-limiting toxicity, but other adverse effects include nausea and vomiting, transient elevations in liver function tests, neurotoxicity, and SIADH. 

Cisplatin has major antitumor activity in a broad range of solid tumors, including non-small cell and small cell lung cancer, esophageal and gastric cancer, head and neck cancer, and genitourinary cancers, particularly testicular, ovarian, and bladder cancer. When used in combination regimens with vinblastine and bleomycin or etoposide and bleomycin, cisplatin-based therapy has led to the cure of nonseminomatous testicular cancer. 

Vincristine [vin KRIS teen] and vinblastine [vin BLAST een] are structurally-related compounds derived from the periwinkle plant, Vinca rosea. They are therefore referred to as the vinca alkaloids. A structurally related new (and less toxic) agent, vinorelbine [vye NO rel been] shows promise in the treatment of advanced non-small cell lung cancer. 

An MAA for vinflunine (Javlor ) 43 (Pierre Fabre) has been submitted to the European Medicines Agency (EMEA) for the treatment of various cancers.103 Pierre Fabre had been developing vinflunine 43104 106 in the USA in partnership with Bristol-Myers Squibb for the treatment of breast, bladder and lung cancers but development was halted in late 2007.107 Four Vinca-type alkaloids have been approved for cancer treatment vinblastine 44108 and vincristine... 

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. 

The vinca alkaloids, vincristine and vinblastine, inhibit tumor growth by destroying microtubules which are essential for cell structure and mitosis. They differ in that vinblastine "blasts" bone marrow while vincristine spares marrow. Vincristine however, causes peripheral neuropathy which is manifested by decreased reflexes, foot drop, weak fingers and decreased autonomic function. Another vinca alkaloid, vindesine is being investigated for the treatment of nonsmaU cell lung cancers. Vindesine causes both marrow suppression and neurotoxicity. 

Vinorelbine tartrate (Fig. 42.35) is used alone or in combination with cispiatin for first-line treatment of nonsmall cell lung cancer. This semisynthetic alkaloid is unique in having oral bioavailability (85), but it currently is available only for IV injection. The initial phase elimination half-life is on par with that observed for vincristine and vinblastine, and the terminal phase half-life is between 28 and 44 hours. Although dose-limiting granulocytopenia is the major adverse effect, potentially fatal interstitial pulmonary changes have been noted, and patients with symptoms of respiratory distress should be promptly evaluated. As with all vinca alkaloids, elimination is primarily hepatobiliary, and dosage reduction should be considered in patients with liver dysfunction. 

P388, murine lymphocytic leukemia UlSO-BCA and BC-l, breast cancer UlSO-COL 2 and COL-2, colon cancer U1S0-LUC I and LU-1, lung cancer UlSO-MEL-2 and MEL-2, melanoma HT<1080 and HT. fibrosarcoma KB, oral epidermoid KB-V, multi drug-resisiani KB KB-3, oral epidermoid carcinoma KB-Vi, durg-resistant KB3 KB-Vi (-fVLB) and KB-VI (-vLB). KB3 in die presence and absence of vinblastine, respectively A 431. epidermoid carcinoma LNCaP, prostate cancer ZR-7S-I, hormone-dependent breast cancer U-373, gliobastoma. 

Phenytoin Phenobarbital Vinblastine Carmustine Methotrexate Lung cancer with brain metastases Phenytoin ieveis feii from 9.4 to 5.6 micrograms/mL 24 hours after vinblastine. Patient fitted. Phenytoin ieveis returned to normai 2 weeks after chemotherapy. Phenobarbitai ieveis unaffected. 4... 

Vinblastine analog Burroughs Well come product, Navelbine, has been approved for treatment of nomsmail cell lung cancer. 

Soon after clinical impact of these phytochemicals in curative and palliative cancer chemotherapies, a number of studies focused on design of their semisynthetic derivatives were developed. These efforts led to important anticancer agents, including vindesine (21), vinorelbine (22), and vinilunine (23). Vinorelbine has been administered for treating non-smaU ceU lung cancer (NSCLC), metastatic breast cancer, and rhabdomyosarcoma [98], Vindesine is usually used to treat leukemia, lymphoma, melanoma, and breast and lung cancers. Vinflunine is a fluoiinated vinblastine derivative and has been submitted to phase III clinical studies in patients with NSCLC and bladder cancer [99]. 

Cisplatin, combined with bleomycin and vinblastine or etoposide, produces cures in most patients with metastatic testicular cancer or germ cell cancer of the ovary. Cisplatin also shows some activity against carcinomas of the head and neck, bladder, cervix, prostate, and lung. 

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