Kimura, H., Yamamoto, N., Shirai, T., Nishida, H., Hayashi, K., Tanzawa, Y., . . . Tsuchiya, H. (2015). Efficacy of triplet regimen antiemetic therapy for chemotherapy-induced nausea and vomiting (CINV) in bone and soft tissue sarcoma patients receiving highly emetogenic chemotherapy, and an efficacy comparison of single-shot palonosetron and consecutive-day granisetron for CINV in a randomized, single-blinded crossover study. Cancer Medicine, 4, 333–341. 

To evaluate the efficacy of combination antiemetic therapy including 5HT3 receptor antagonists, neurokinin-1 (NK1) receptor antagonists, and dexamethasone for multiple highly emetogenic anticancer agents in patients with bone and soft tissue sarcoma; to compare the effectiveness of single-shot palonosetron and consecutive-day granisetron

A single randomization method was used to assign eligible patients to the palonosetron or granisetron arm. Patients in the palonosetron arm received a palonosetron regimen during the first and third chemotherapy courses and a granisetron regimen the second and fourth courses. Patients in the granisetron arm received granisetron during the first and third courses and palonosetron the second and fourth. All patients received an NK1 receptor antagonist and dexamethasone. Patients receiving the palonosetron regimen were administered 0.75 mg of palonosetron on day 1, and patients receiving the granisetron regimen received 3 mg of granisetron twice daily on days 1–4 and once on day 5. Patients were followed for 10 days during each course for efficacy and safety endpoints. On days 4 and 10, patients responded to a questionnaire about emetic experiences and rescue medication use. Nausea severity was rated from 0–10 according to subjective assessments during the acute and delayed phases.

• N = 24
• MEAN AGE = 43.4 eyars (range = 15–70 years)
• MALES: 50%, FEMALES: 50%
• KEY DISEASE CHARACTERISTICS: Nine patients with osteosarcoma; eight with malignant fibrous histiocytoma; two with leiomyosarcoma; five with other bone or soft tissue sarcomas; receiving highly emetogenic chemotherapy

• SITE: Single site    
• SETTING TYPE: Not specified  
• LOCATION: Japan

• PHASE OF CARE: Active antitumor treatment

Randomized, single-blinded crossover study

• No specific instruments were listed for the questionnaire (which included number of emetic episodes, use of rescue therapy, nausea severity rated on scale of 0–10, and patient’s preferred regimen).
• Toxicity data were graded according to Common Terminology Criteria for Adverse Events (CTCAE)-adapted toxicity grades.

The overall complete response rate was 66 out of 96 courses (69%) for the acute phase, 38 out of 96 (40%) for the delayed phase, and 33 out of 96 (34%) overall. In the acute phase, complete responses were achieved in 34 out of 48 courses (71%) of the palonosetron regimen and 33 out of 48 courses (69%) of the granisetron regimen. In the delayed phase, complete responses were achieved in 18 courses (38%) of the palonosetron regimen and 20 courses (42%) of the granisetron regimen. There were no statistically significant differences in complete responses for either regimen. Patient preference was recorded for 15 patients. Two patients (13%) preferred palonosetron, three patients (20%) preferred granisetron, and 10 patients (67%) reported that both antiemetic regimens had similar efficacies. The amount of time till the first administration of rescue therapy tended to be longer in the granisetron regimen (5.65 days) compared to palonosetron (5.12 days), but this was not statistically significant (p = 0.115). For palonosetron, regimen rescue therapy was administered in 24 out of 48 courses compared to 17 out of 48 courses for the granisetron regimen. Nausea severity was slightly greater with granisetron (3.58 acute phase, 4.04 delayed) than palonosetron (3.40 acute phase, 3.92 delayed), but this was not statistically significant.

Antiemetic therapy with a three-drug combination was not sufficient to control chemotherapy-induced nausea and vomiting during chemotherapy with multiple highly emetogenic chemotherapy agents for bone and soft tissue sarcoma. However, consecutive-day granisetron was not inferior to single-shot palonosetron for treating chemotherpy-induced nausea and vomiting.

• Small sample (< 30)
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Other limitations/explanation: Did not use National Comprehensive Cancer Network-recommended dosage of dexamethasone for highly emetogenic chemotherapy (12 mg on day 1 and 8 mg daily on subsequent days [study used 6.6 mg daily])

This study demonstrated that granisetron given in consecutive-day dosing was not inferior to single-dose palonosetron in triplet therapy for highly emetogenic chemotherapy in patients with bone or soft tissue sarcoma. However, neither combination therapy was adequate to control chemotherapy-induced nausea and vomiting in this population. The development of novel antiemetic agents, or new combination therapies with existing agents such as olanzapine, was recommended. The appropriate dosing of all agents in combination therapy is an important consideration.