Vincristine lung cancer

Nitrogen mustard is clinically used for the treatment of lymphomas and some forms of lung cancer. The major indication for mechlorethamine is Hodgkin s disease as a part of the MOPP regimen (mechlorethamine + vincristine (oncovin) + procarbazine + prednisone). The usual dose consists of 6 mg/m2 on days 1 and 8. This drug has pronounced hematological toxicity (myelo-suppression). 

The vesicant vinorelbine is structurally similar to vincristine and may cause many of the same side effects as vincristine. While this vesicant is administered intravenously over 6 to 10 minutes, patients should be counseled about neuropathy, ileus, and myelosuppression. The pharmacokinetics of vinorelbine are best described by a three-compartment model, with an a half-life of 2 to 6 minutes, a 3 half-life of 1.9 hours, and a y half-life of 40 hours. Vinorelbine has shown efficacy in the treatment of breast cancer and non-small cell lung cancer. Additional side effects include myelosuppression, paresthesias, and mild nausea and vomiting. 

POC Procarbazine, vincristine, cyclophosphamide Melanoma, small cell lung cancer... 

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. 

In vitro studies with several tumor cell lines have shown vitamin C to enhance the cytotoxic activity of doxorubicin, cisplatin, paclitaxel, dacarbazine, 5-FU, and bleomycin. Vitamin C has also been shown to increase drug accumulation and to partially reverse vincristine resistance of human nonsmall-cell lung cancer cells. 

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... 

Vincristine (Onco-TCS) Lung cancer Inex Pharm II... 

Caelyx is liposomal doxorubicin very well used as a treatment of choice for a number of cancers with good tolerability and antitumor activity, as has been demonstrated in many phase I or II clinical trials. One such example is the conduct of phase I study of Caelyx (PEGylated liposomal doxorubicin, 25 M) mg/m2) in combination with cyclophosphamide (750-1000 mg/m2) and vincristine (1.2 mg/m2) every 21 days in patients with relapsed or refractory small cell lung cancer [442], The suggested doses were CaelyxTM 35 mg/m2, cyclophosphamide 750 mg/m2, and vincristine 1.2 mg/m2 intravenously every 21 days. This combination was well tolerated... 

Leighl, N., Burkes, R. L., Dancey, J. E., Lopez, P. G., Higgins, B. P., Walde, P L. D., Rudinskas, L. C., Rahim, Y. H., Rodgers, A., Pond, G. R., and Shepherd, F. A. (2003), A phase I study of pegylated liposomal doxorubicin (Caelyx ) in combination with cyclophosphamide and vincristine as second-line treatment of patients with small-cell lung cancer, Clin. Lung Cancer, 5,107-112. 

MUd to moderate reduction in creatinine clearance with rises in serum urea and creatinine were reported in 14% of patients receiving carboplatin in a dose of 400 mg/m for gynecological malignancies. Of the patients who received carboplatin 400 mg/m with vincristine but without hydration for lung cancer, 19% developed renal changes. 

Leighl NB +, Clin Lung Cancer 5(2), 107 (with doxorubicin and vincristine)... 

Roth BJ, Johnson DH, Einhorn LH, et al. Randomized study of cyclophosphamide, doxorubicin, and vincristine versus etoposide and cisplatin versus alternation of these two regimens in extensive small-cell lung cancer A phase III trial of the Southeastern Cancer Study Group. J Clin Oncol 1992 10 282-291. 

Reck M, von Pawel J, Macha HN, et al. Randomized phase III trial of paclitaxel, etoposide, and carboplatin versus carboplatin, etoposide, and vincristine in patients with small-cell lung cancer. J Natl Cancer Inst 2003 95 1118-1127. 

VINCRISTINE is given i.v. once weekly in a dose of 1-2 mg/m in combination with other cytostatics in the treatment of leukaemia, malignant lymphoma and lung cancer. 

The Eli Lilly company developed several series of derivatives with modifications in the vindoline part of the dimeric structure, culminating with the approval of vindesine, Fig. (1), for clinical treatments. Vindesine, with the commercial name Eldisine and Enisone , has a vincristine-like spectrum of activity, and is used mainly in the treatment of melanoma, acute lymphoblastic leukaemia and advanced non-small cell lung cancer [13, 14, 16]. Vindesine is approved in Europe and other areas but, in the United States, vindesine is approved only for investigational use [15]. 

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. 

Gandhi L, Harding MW, Neubauer M, Langer CJ, Moore M, Ross HI et al. A phase II study of the safety and efficacy of the multidrug resistance inhibitor VX-710 combined with doxorubicin and vincristine in patients with recurrent small cell lung cancer. Cancer 2007 109 924-932. 

The efficacy of doxorubicin can be increased by verapamil and nicardipine in doxorubicin-resistant tissue culture systems, while nifedipine has only minimal activity. A study in five patients with small cell lung cancer given doxorubicin, vincristine, etoposide and cyclophosphamide showed that when they were given verapamil 240 to 480 mg daily the AUC of doxorubicin was doubled, its peak serum levels were raised and its clearance was reduced. No increased toxicity was seen in this study. However, although another study found no increase in non-cardiac toxic-ities, verapamil caused an unacceptable degree of cardiac toxicity. Be alert for this possibility if both drugs are used. 

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