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Phase I study of continuous-infusion PALA and 5-FU
Cancer Treatment Reports
|March 1, 1984
Summary
This study investigated PALA and 5-FU chemotherapy for refractory malignancies. While toxicities were observed, limited therapeutic responses occurred, suggesting further research into optimal dosing and combinations.
Area of Science:
- Oncology
- Pharmacology
- Cancer Therapeutics
Background:
- Conventional therapies often fail in advanced malignancies.
- Novel combination chemotherapy regimens are needed for refractory cancers.
Purpose of the Study:
- To evaluate the efficacy and toxicity of PALA and 5-FU combination therapy.
- To assess the correlation between PALA's biochemical effects and clinical response.
Main Methods:
- Eighteen patients with refractory malignancies received 5-day continuous infusions of PALA and 5-FU.
- Doses were PALA 940 mg/m2/day and 5-FU 180-325 mg/m2/day, repeated every 3-4 weeks.
- Leukocyte L-aspartate transcarbamylase (ATCase) activity and plasma PALA levels were monitored.
Main Results:
- Mucositis and diarrhea were dose-limiting toxicities; skin rashes, nausea, and vomiting were also observed.
- Peak plasma PALA concentrations of ~20 microM correlated with 90% ATCase inhibition.
- Two patients (one colon, one mammary carcinoma) showed therapeutic responses, not correlated with ATCase depression.
Conclusions:
- PALA and 5-FU combination therapy shows limited efficacy in refractory malignancies.
- Further investigation into lower PALA doses (250 mg/m2) for ATCase inhibition is warranted.
- A Phase II trial is planned to explore PALA with escalating 5-FU doses.