Vinorelbine

Abstract

Vinorelbine is a semisynthetic vinca alkaloid with a broad spectrum of antitumour activity. The drug is effective as a single agent in inoperable/advanced non-small cell lung cancer (NSCLC), producing objective response rates of about 15 to 30%, and as first-line or later chemotherapy for metastatic spread in advanced breast cancer. Combining vinorelbine with standard chemotherapeutic regimens improves response rates in these indications compared with vinorelbine monotherapy: in NSCLC response rates increase to 30 to 50% when vinorelbine is administered with cisplatin. Importantly, survival was prolonged by a further 9 weeks with this combination in a trial in > 600 patients with NSCLC. Comparative trials evaluating vinorelbine in women with advanced breast cancer are few at present. However, results suggest greater efficacy for vinorelbine than for melphalan as second-line chemotherapy, and similar efficacy for vinorelbine plus doxorubicin compared with doxorubicin plus 2 other drugs as first-line chemotherapy. Vinorelbine has tended to yield superior response rates when compared with vindesine, and appears to have greater haematological toxicity (i.e. granulocytopenia) but less neurological toxicity (peripheral neuropathy, constipation, loss of deep tendon reflexes) than this agent. Myelosuppression is the most frequent cause of vinorelbine treatment delay or dose reduction. Other consequences of vinorelbine therapy are those typically seen with antineoplastic agents, such as diarrhoea, nausea and vomiting, and alopecia. However, these are rarely severe. Early clinical investigations indicate that the antitumour effects of vinorelbine in other malignancies including ovarian carcinoma, lymphoma and head and neck cancer warrant further exploration, as does the efficacy of the drug relative to standard approaches and its possible beneficial effects on quality of life of cancer patients. Clarification is also required of the feasibility of an oral dosage form, which in preliminary investigations has shown some efficacy in NSCLC, but a variable response rate and high incidence of gastrointestinal disturbances in women with breast cancer. Thus, vinorelbine as a single agent or combined palliative therapy is effective against advanced NSCLC, and as first- or second-line chemotherapy in advanced breast cancer. This semisynthetic vinca alkaloid has a manageable tolerability profile and potential for use in other malignancies and as an oral formulation. With these attributes, vinorelbine is a valuable option which extends the range of treatments available for these difficult-to-treat malignancies.

Vinorelbine in the Treatment of Non-Small Cell Lung Cancer

“…Serum bilirubin and liver enzyme levels (AST/ALT) increased transiently during vinorelbine therapy [61]., and dosage adjustments are recommended according to serum bilirubin measurements. The usual vinorelbine dose (30 mg/m 2 ) should be decreased to 15 mg/m 2 for total serum bilirubin levels of 21 to 30 mg/L and to 7.5 mg/m 2 for levels >30 mg/m 2 [62]. There are no specific precautions for patients with renal insufficiency.…”

Synthesis, Antiproliferative Evaluation, and Structure–Activity Relationships of 3‐Arylquinolines

“…[1][2][3] A tricyclic structural pattern, such as a 2-phenyl-naphthalene scaffold (1), is present in a large number of antineoplastic compounds. [4][5][6][7][8] While the simple scaffold alone may not be a potent pharmacophore, derivatives with appropriate substitution patterns on both ring systems could exhibit potent biological activities.…”

“…Thirty-four compounds substituted with various substituents (NO 2 , F, Cl, Br, CH 3 and OMe), selected primarily for their wide range of electronic properties (s = + 0.78 to À0.36), using different substitution patterns were designed, synthesized and evaluated for their antiproliferative activity in vitro.…”

“…Dihaloganated A-ring systems gave similar results, for example, compound 33 showed significant decrease in activity compared to compound 37. Replacement of electron-donating groups with electron-withdrawing substituents at the R 3 result- www.chemmedchem.org ed in a moderate to significant decrease in activity, in the order NO 2 > F > Cl > Br > CH 3 . Of the 34 compounds tested, potent activities were noted for analogues 36, 37, 38 and 40, but the most potent activity was found with compounds 41, whose IC 50 values against the three human tumor cell lines ranged from 0.59 to 0.21 mm, which is more potent than the known antitumor agent, 5-FU (Table 1).…”

Identification of the Major Degradation Products of Vinorelbine by Frit-FAB LC/MS and NMR

“…2 Vinorelbine (5′-nor-anhydrovinblastine, 1, Fig. 1) shares a similar dimeric structure composed of catharanthine and vindoline moieties with vincristine and vinblastine.…”