Can Cisplatin and Pemetrexed Cause Constipation?
Yes, cisplatin and pemetrexed can cause constipation, though it is not among the most common or severe toxicities associated with this combination regimen.
Evidence from Clinical Trials
The combination of cisplatin and pemetrexed does list constipation as a documented adverse event, though it occurs at relatively low rates:
In a Japanese safety study of bevacizumab plus cisplatin/pemetrexed in malignant pleural mesothelioma patients, constipation (grade 1/2 only) occurred in 71.4% of patients, making it one of the more common gastrointestinal side effects 1.
In a phase III trial comparing docetaxel plus cisplatin regimens for non-small cell lung cancer, grade 3 constipation occurred in 1% of patients and grade 4 constipation in 1% of patients receiving cisplatin-based therapy 2.
More Common Gastrointestinal Toxicities to Anticipate
While constipation can occur, the predominant gastrointestinal toxicities with cisplatin/pemetrexed are nausea, vomiting, diarrhea, dehydration, and stomatitis, which are significantly more frequent and clinically relevant:
Nausea, vomiting, fatigue, diarrhea, dehydration, and stomatitis are significantly higher in the pemetrexed/cisplatin arm compared to cisplatin alone 2.
In the Japanese study, nausea occurred in 85.7% of patients (grade 1/2 only) 1.
The Thorax guidelines specifically note that fatigue, dehydration, and stomatitis are significantly more common with the pemetrexed/cisplatin combination 3.
Clinical Management Approach
When counseling patients about this regimen, prioritize discussion of the more common and severe toxicities:
Hematologic toxicities (neutropenia, anemia, thrombocytopenia) are the most clinically significant, with grade 3-4 neutropenia occurring in 15.1% of patients 2.
Overall, 62% of patients receiving pemetrexed plus cisplatin experience grade 3-4 adverse events 3.
Prophylactic antiemetics are essential, as reflected in the cost analyses showing antiemetic costs of $653.40 per month for cisplatin-based regimens 2.
Common Pitfall
Do not overlook the mandatory vitamin supplementation requirements (folic acid and vitamin B12) when prescribing pemetrexed, as these reduce hematologic toxicity 4, 3. While managing constipation if it occurs, focus monitoring efforts on the more frequent and severe toxicities: myelosuppression, nausea/vomiting, and fatigue.