Indication:
Acute Myeloid Leukemia
Hodgkins disease
New Drugs Approved by (DCI) Drug Controller GENERAL - India For Marketing
(Ref- IDMA Publication)
Name of Drug Indication Date of Approval
Vindesine sulphate Anticancer agent 28-10-1998
Summary-
Vindesine sulphate is a vinca alkaloid which demonstrates promise for a variety of
cancer types, however full extent of activity remains to be examined
It major toxicities are similar to those in the family, myelotoxicity and neurotoxicity
It was recomended for approval by FDAs oncologic Drugs Advisory Committe in
September 1982. A New Drug Application (NDA) is pending
Adverse Reaction:
Side effects
Major dose -limiting toxicities include myelosuppression and neuropathy
The primary hemattological toxicity is leukopenia , which is reversible with dosage
reduction or dsicontinuation.
Anemia and thrombocytoenia occur, but are rarely severe.
Neurotoxicity appears to be a function of cumulative dose. patients with hepatic dysfunction
and those over 60 years old are at greater risk.
Neurotoxic manifestations include peripheral paresthesia , decreased tendon reflexes,
muscle weakness, and myalgia, headche, paratoid, and jaw pain, constipation and
paralytic ileus
Other side effects include -
Nausea, vomiting,stomatitis, hoarseness, transcient hepatic dysfunction, inappropiate
antidiuertic hormone, fever, skin rash, alopecia, local cellulitis,
Vindesine sulfate is a potent vesicant, avoid extravasation into the SC tissues
Pharmacology/ Pharmacokinetics:
Pharmacology-
Vindsine Sulphate (Lily 99094, NSC -245467, DAVA , desacetyl vinblastine amide sulfate)
is a synthetic vince alkaloid derived from vinblastine sulphate , but more closely resembling
the activity of vincristine
A large number of studies suppport its utility in a divers group of cancer types.
Major and dose-limiting toxicities include myelosuppression and neurotoxicity
The mechanism of vindesines anti cancer action is probably like that of the other
vinca alkaloids, it is cell -cycle specific and bocks mitosis with metapase arrest.
Vinca alkaloids bind specifically to cellular microtubes of the mitotic apparatus and
disrupt their function. This leads to inability of the dividing cell to correctely segregate
chromosomes and untimately to cell death.
Pharmacokinetics-
Vindesine sulfate appears to have similar pharmacokinetics to vincristine and vinblastine.
The triphase clearance profile of IV vindsine is summarised below
IV Vindesine clearance
Phase Half-life Volume of distribution
(minutes) ( litres)
Alpha 3+/- 1 5+/- 2
Beta 99+/- 45 58+/- 51
Gamma 1213 +/- 493 598+/- 294
Elimination in urine in the first 24 hours accounts for 13.2% of the total dose administered.
The remainder is sequestered in the body or eliminated in the bile
Clinical trials-
Overall vindesine demonstrates good activity in difficult -to-treat and refractory cancer
types. Responses to vindesine in patients who have received vincristine or vinblastine
therapy suggest a lack of cross resistence between these agents
Doses ranged from 3 to 4.5 mg/m2 as an IV bolus every 1 to 2 weeks or 1 to 2mg/m2 day
for 2 to 10 days every 2 to 3 weeks. The results are summarised -
Vindesine clinical studies
Cancer type No of Patients Response rate
Range % Average% Complete No
patients
Lung 234 17-43 30 10
Esophageal 76 17-55 43 0
Colorectal 33 6 6 1
Metastatic 120 0-28 18 0
breast
Lymphoma 61 34-50 41 4
Leukemias 26 15-61 38 4
TOTAL 550 0-61 29 19
Manufacturer Details