Evaluation of the Incidence of Nausea and Vomiting in Patients With Colorectal Cancer Receiving Irinotecan-based Therapy
Evaluation of the Incidence of Nausea and Vomiting in Patients With Colorectal Cancer Receiving Irinotecan-based Therapy
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.
Inclusion Criteria:

 -  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
 chemotherapy:

 -  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

 Exclusion Criteria:

 -  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