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Advances in vinca-alkaloids: Navelbine
1Institut de Recherche sur les Leucémies et les Maladies du Sang, Service d'Oncologie Médicale, Hôpital Saint-Louis, Paris, France.
Nouvelle Revue Francaise D'Hematologie
|January 1, 1989
Summary
Vinorelbine (NVB) is a novel vinca alkaloid demonstrating significant antitumor activity in preclinical models and human cancers. Its manageable toxicity profile, primarily neutropenia, supports its clinical utility in treating various malignancies.
Area of Science:
- Oncology
- Pharmacology
- Medicinal Chemistry
Background:
- Vinorelbine (NVB) is a semisynthetic vinca alkaloid derived from vinblastine.
- It features chemical modifications on the catharantine moiety, distinguishing it from parent compounds.
- Preclinical studies indicated promising antitumor activity against various cancer models.
Purpose of the Study:
- To evaluate the antitumor activity and toxicity profile of Vinorelbine (NVB).
- To assess the clinical efficacy of NVB in patients with non-small cell lung cancer, advanced breast cancer, and Hodgkin's disease.
Main Methods:
- Preclinical evaluation in murine tumors, human cell lines, and xenografts.
- Acute, subacute, and chronic toxicity studies in rodents, dogs, and primates.
- Phase I and II clinical trials in human patients.
Main Results:
- Hematotoxicity (neutropenia) was the primary dose-limiting side effect in humans.
- NVB demonstrated limited neurotoxicity and other manageable side effects like mild emesis and alopecia.
- Phase II trials showed significant response rates: 33% in non-small cell lung cancer, 53% in advanced breast cancer, and 90% in Hodgkin's disease.
Conclusions:
- Chemical modification of vinca alkaloids can yield agents with broad-spectrum activity and improved safety.
- Vinorelbine exhibits promising efficacy and a manageable toxicity profile, supporting its use in cancer therapy.