Related Experiment Videos
Combination high-dose etoposide and vincristine infusion
D V Jackson1, J M Cruz, D R White
1Cancer Center of Wake Forest University, Winston-Salem, NC 27103.
Investigational New Drugs
|January 1, 1990
Summary
This study explored etoposide and vincristine chemotherapy in cancer patients. Higher etoposide doses increased toxicity, with 500 mg/m2 recommended for future trials.
Area of Science:
- Oncology
- Clinical Pharmacology
Background:
- Preclinical studies identified a synergistic antitumor effect between etoposide and vincristine in murine models.
- This prompted clinical investigation of the drug combination for cancer treatment.
Purpose of the Study:
- To evaluate the safety and efficacy of escalating doses of etoposide in combination with a fixed dose of vincristine.
- To determine the recommended starting dose for etoposide in this combination regimen for further clinical trials.
Main Methods:
- A phase I clinical trial was conducted with 26 patients.
- Etoposide was administered at four dose levels (250, 500, 750, 1,000 mg/m2) in divided daily fractions over 3 days.
- Vincristine was given as two fixed infusions between etoposide doses.
Main Results:
- Myelosuppression, particularly Grade 4 white blood cell toxicity, increased with higher etoposide doses.
- Incidence of life-threatening infections also correlated with escalating etoposide dosage.
- Objective responses were noted in refractory Hodgkin's disease and immunoblastic lymphoma; stable disease was observed in lung adenocarcinoma and Hodgkin's disease.
Conclusions:
- The combination of etoposide and vincristine demonstrated antitumor activity but was associated with dose-dependent myelosuppression and infection risk.
- A starting dose of 500 mg/m2 of etoposide, fractionated over 3 days, is recommended for future studies, with potential for dose escalation.