Takatori, E., Shoji, T., Miura, Y., Nagao, M., Takada, A., Nagasawa, T., . . . Sugiyama, T. (2015). A phase II clinical trial of palonosetron for the management of delayed vomiting in gynecological cancer patients receiving paclitaxel/carboplatin therapy. Molecular and Clinical Oncology, 3, 281–286. 

To evaluate the efficacy of palonosetron plus dexamethasone in controlling delayed chemotherapy-induced nausea and vomiting (CINV) in patients with gynecologic cancer receiving paclitaxel and carboplatin (a moderately emetogenic protocol)

On day 1 of therapy, palonosetron at 0.75 mg/body IV and dexamethasone at 19.8 mg/body IV were administered. On days 2 and 3, dexamethasone at 6.6 mg/body in 100 ml of normal saline IV was given. Patients were administered the Multinational Association of Supportive Care in Cancer Antiemesis Tool to complete on days 1–8. Only the first cycle of this protocol was evaluated. The patients rated the intensity of nausea using a Visual Analog Scale scored as mild (1–2), moderate (3–4), or severe (≥ 5).

• N = 42
• MEDIAN AGE = 60.5 years (range = 32–83 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Gynecologic cancers including cervical, endometrial, and ovarian
• OTHER KEY SAMPLE CHARACTERISTICS: Naïve to chemotherapy; aged ≥ 20 years; receiving a regimen of paclitaxel and carboplatin every three weeks; Eastern Cooperative Oncology Group performance status of 0–2; laboratory results related to bone marrow and hepatic and renal functions met criteria for chemotherapy infusion

• SITE: Not stated 
• SETTING TYPE: Not specified  
• LOCATION: Japan

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Elder care and palliative care

Phase 2, nonrandomized, prospective, nonblinded clinical trial

• Self-completion of the Multinational Association of Supportive Care in Cancer (MASCC) antiemesis tool
• Visual Analog Scale (VAS) to measure intensity of nausea
• Complete response (CR) was defined as no vomiting, no additional antiemetic use, and no rescue therapy.  
• Complete control (CC) was defined as complete control of vomiting with no antiemetic use, only mild nausea, and no rescue therapy.
• Subgroup analyses were performed to comparatively assess the delayed CR rates by age (≥ 55 years versus < 55 years), body surface area (≥ 1.47 m² versus < 1.47 m²), performance status (0 versus 1–2), and complications (present versus absent).

The CR rate for the acute period (0–24 hours) was 95.2%, or 40 out of 42 patients. In the delayed period (24–96 hours), a CR of 90.5%, or 38 out of 42 patients, was reported. Overall, the CR rate was 85.7%, or 36 out of 42 patients. The CC rate for the acute period was 90.5%, or 38 out of 42 patients. For the delayed period, it was 85.7%, or 36 out of 42 patients. The CC rate was 78.6%, or 33 out of 42, overall. Nausea was reported in the acute, delayed, and overall periods by four, seven, and nine patients respectively. The average overall nausea score for the nine patients who reported nausea was 3.69+ 2.77 on a five-point VAS scale. Rescue antiemetics were used by two patients in the acute phase, four patients in the delayed phase, and in six patients overall. Granisetron and dexamethasone were the most commonly used rescue antiemetics. Adverse events were minimal with 16 patients experiencing constipation, three headache, and two diarrhea.

This trial supported the use of palonosetron over other 5HT3 receptor antagonists for the prevention of CINV in the 24–96-hour period following therapy in female patients with gynecologic malignancies. These data also support evidence that it is difficult to achieve CR for nausea as nine (20%) of the patients in this study experienced nausea.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding) 
• Risk of bias (no random assignment) 
• Risk of bias (no appropriate attentional control condition) 

Palonosetron was especially helpful in the prevention of CINV during the delayed phase of moderately emetogenic chemotherapy. This study also measured nausea, which was helpful because many studies primarily address vomiting even though nausea often creates more patient distress.