Dolasetron Mesylate and Dexamethasone With or Without Aprepitant in Preventing Nausea and Vomiting in Patients Undergoing Oxaliplatin-Containing Chemotherapy for Gastrointestinal Malignancy
Dolasetron Mesylate and Dexamethasone With or Without Aprepitant in Preventing Nausea and Vomiting in Patients Undergoing Oxaliplatin-Containing Chemotherapy for Gastrointestinal Malignancy
This randomized pilot clinical trial dolasetron mesylate and dexamethasone with or without
 aprepitant in preventing nausea and vomiting in patients undergoing oxaliplatin-containing
 chemotherapy for gastrointestinal malignancy. Antiemetic drugs may help lessen or prevent
 nausea and vomiting in patients treated with chemotherapy. It is not yet known whether giving
 aprepitant together with dolasetron mesylate and dexamethasone is more effective than
 dolasetron mesylate and dexamethasone alone in preventing nausea and vomiting.
PRIMARY OBJECTIVES:

 I. To estimate the incidence and severity of acute and delayed nausea and vomiting associated
 with oxaliplatin-containing regimens in patients with gastrointestinal (GI) malignancy.

 II. To estimate the percent of patients who have experienced nausea and vomiting with their
 first or second cycle of oxaliplatin-containing regimen, and would consent to randomization
 to standard antiemetic therapy with or without aprepitant.

 III. To obtain preliminary data on the safety and efficacy of aprepitant, in combination with
 dolasetron (dolasetron mesylate) and dexamethasone, in patients receiving
 oxaliplatin-containing regimen.

 IV. To report on medication compliance with antiemetic medications (dexamethasone and
 aprepitant or placebo) scheduled to be taken at home on days 2 and 3 for all randomized
 patients (day 1 = day of treatment).

 OUTLINE: Patients receive standard antiemetics comprising dolasetron mesylate orally (PO) or
 intravenously (IV) and dexamethasone PO or IV during course 1 of oxaliplatin-containing
 chemotherapy. Patients experiencing any grade 1-4 nausea and vomiting* are randomized to 1 of
 2 treatment arms.

 ARM I: Patients receive dolasetron mesylate PO or IV, dexamethasone PO or IV, and aprepitant
 PO 1 day before chemotherapy and dexamethasone PO and aprepitant PO on days 2 and 3 after
 chemotherapy begins during course 2-3.

 ARM II: Patients receive dolasetron mesylate and dexamethasone as in Arm I and placebo PO 1
 day before chemotherapy and dexamethasone PO and placebo PO on days 2 and 3 after
 chemotherapy begins during courses 2-3.

 In both arms, treatment continues in the absence of unacceptable toxicity.

 NOTE: * Patients not developing nausea and vomiting until the second course of treatment are
 also randomized during courses 3 and 4 of chemotherapy.

 After completion of study treatment, patients are followed up periodically.
Inclusion Criteria:

 -  Patients who have a diagnosis of GI malignancy and who are scheduled to receive their
 initial treatment with an oxaliplatin-containing regimen in combination with
 5-fluorouracil; these include combinations such as fluorouracil, oxaliplatin, and
 leucovorin calcium (FOLFOX), FOLFOX + bevacizumab, FOLFOX + cetuximab

 -  Standard antiemetic therapy with initial treatment must include the dolasetron and
 dexamethasone; the minimum adequate doses include either:

 -  Dolasetron (Anzemet) 100mg PO/IV or 1.8mg/kg IV AND

 -  Dexamethasone (Decadron) 10mg PO/IV

 -  Patient must agree, as part of the informed consent, to keep a journal of the episodes
 of nausea, vomiting, retching, and amount of rescue medications used on days 1 to 5
 (day 1 = day of treatment)

 -  Signed informed consent

 Exclusion Criteria:

 -  Allergy or intolerance to dolasetron and dexamethasone

 -  Use of another antiemetic agent (5HT3 antagonists, phenothiazines, butyrophenones,
 cannabinoids, metoclopramide, or corticosteroids) within 72 hours of day 1 of the
 study

 -  An episode of vomiting or retching within 24 hours before the start of the initial
 treatment with oxaliplatin-containing regimen

 -  Severe concurrent illness other than neoplasia

 -  Gastrointestinal obstruction or an active peptic ulcer

 -  Radiation therapy to the abdomen or pelvis within 1 week before or after day 1 of the
 study

 -  Absolute neutrophil count of less than 1.5 x 10^9/L (unless physician approves to
 proceed with chemotherapy) or

 -  Platelets less than 100 x 109/L (unless physician approves to proceed with
 chemotherapy)

 -  Total bilirubin > 2 x upper limits of normal

 -  Patients who are pregnant or breast feeding

 -  Patients who are non-English speaking

 -  Patients with cancer-induced nausea and vomiting grade 1 or greater using the Common
 Terminology Criteria for Adverse Events (CTCAE) version 3.0 criteria