This is a study to determine how much nausea and or vomiting is caused by irinotecan-based
chemotherapy in patients with colorectal cancer. Patients with colorectal cancer scheduled
to receive their first cycle of an irinotecan-based chemotherapy regimen are eligible. Any
chemotherapy agents administered in combination with irinotecan must have low-minimal
potential to cause nausea and or vomiting. Examples of acceptable regimens would be
irinotecan in combination with infusional fluorouracil and leucovorin (FOLFRI) with or
without bevacizumab and irinotecan in combination with cetuximab. Patients who have received
prior non-irinotecan-based chemotherapy are eligible providing they experienced no vomiting
and no greater than mild nausea with their prior chemotherapy.
Irinotecan is a camptothecin analog which exerts its cytotoxic effects by forming a covalent
complex with topoisomerase I and DNA, resulting in inhibition of DNA re-ligation,
accumulation of DNA double strand breaks and apoptotic cell death (1). Irinotecan is FDA
approved for use in the front-line and second-line treatment of colorectal cancer. It has
also demonstrated activity in a variety of other non-hematologic tumors. The recently
updated ASCO antiemetic guidelines characterize irinotecan as having moderate emetic risk.
(2). However, the emetogenic potential of this agent has been poorly characterized and there
are no published prospective trials with emesis as a primary-end point. In addition there is
a complete paucity of information on the potential of irinotecan to induce emesis beyond the
first day after chemotherapy, so-called delayed emesis. Best characterized following
cisplatin, delayed emesis is also associated with a number of other chemotherapy agents that
similar to irinotecan appear to be moderately emetogenic such as carboplatin,
cyclophosphamide and doxorubicin. Antiemetic prophylaxis for delayed emesis following
irinotecan is not routinely prescribed at the present time. Prospectively obtained
information on the potential of irinotecan to cause delayed emesis would be helpful in
guiding appropriate antiemetic practice.
- Patients with colorectal cancer receiving irinotecan in combination with infusional
fluorouracil and leucovorin (FOLFRI) with or without bevacizumab or irinotecan in
combination with cetuximab
- All patients will receive the following standard antiemetic regimen prior to
- Dexamethasone 8 mg PO/IV
- An approved dose of a 5HT3 receptor antagonist. Ondansetron 8mg IV or 24mg PO
Dolasetron 100mg IV/PO Granisetron 1 mg IV or 2mg PO Use of palonosetron will be
excluded on this trial No routine prophylaxis for delayed emesis will be given.
Patients will be instructed in the use of rescue antiemetics if needed.
- Minimum age of 18 years.
- Premenopausal patients must demonstrate a negative serum or urine pregnancy test
prior to receiving chemotherapy.
- ECOG performance status of 0-2 (Appendix A)
- Execution of written informed consent
- Patients with history of moderate-severe nausea or any vomiting with prior
chemotherapy including irinotecan based chemotherapy.
- Concomitant use of any drug with potential antiemetic efficacy (Appendix B) 24 hours
before chemotherapy and during the 120 hour study period. Chronic use (more than 2
weeks) of benzodiazepines is allowed.
- Vomiting, retching or nausea (NCI > 1) in the 24 hours preceding chemotherapy
- Palliative surgery < 2 weeks from study entry
- Concurrent radiotherapy