Dolasetron Mesylate and Dexamethasone With or Without Aprepitant in Preventing Nausea and Vomiting in Patients Undergoing Oxaliplatin-Containing Chemotherapy for Gastrointestinal Malignancy

A Pilot Study to Evaluate the Safety and Efficacy of Aprepitant in Combination With Dolasetron and Dexamethasone for the Prevention of Nausea and Vomiting Following Oxaliplatin-containing Regimen Which Includes 5-FU.

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