Longo, F., Mansueto, G., Lapadula, V., Stumbo, L., DelBene, G., Adua, D., … Quadrini, S. (2012). Combination of aprepitant, palonosetron and dexamethasone as antiemetic prophylaxis in lung cancer patients receiving multiple cycles of cisplatin-based chemotherapy. International Journal of Clinical Practice, 66, 753-757.

To evaluate whether the antiemetic efficacy of triple combination aprepitant, palonosetron, and dexamethasone could be sustained for up to six cycles of highly emetogenic chemotherapy (HEC) (cisplatin ≥ 50 mg/m²)

To be eligible, patients had to be chemotherapy-naïve adults with lung cancer, have an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0–2, and be receiving 4–6 cycles platinum-based therapy (cisplatin ≥ 50 mg/m²).

All eligible patients received 125 mg oral aprepitant, 0.25 mg IV palonosetron, and 20 mg IV dexamethasone before chemotherapy on day 1, and 80 mg oral aprepitant and 4 mg oral or intramuscular dexamethasone on days 2 and 3. Patients recorded all vomiting episodes, any use of rescue medication, and the severity of nausea on 4-point Likert-type scale in diaries for 5 days (0–120 hours) after chemotherapy during all planned cycles.

• The study began with 156 patients, and 118 completed the study.
• The median age of participants was 64 with a range of 33–81.
• The sample was 77% male and 23% female.
• Cancer staging was 74% stage IV and 12% stage IIIb.
• Cisplatin dosing was 46% 75 mg/m²and 41% 80 mg/m².  Patients receiving cisplatin combined with two other drugs represented 87% of the sample.
• Number of chemotherapy cycles planned was 6 cycles (80%) and 4 cycles (18%). The majority (84%) completed their planned cycles.
• Patients were excluded if they had
  • Emesis within 24 hours before starting chemotherapy
  • Noncontrolled metastasis in the brain
  • Previous radiation to the brain, abdomen, or pelvis
  • Concomitant medication with antiemetic activity or known to induce cytochrome P450 enzymes.

The study was conducted at multiple outpatient sites in Italy.

All patients were in active antitumor treatment.

This was a prospective observational study.

• Patients maintained study-specific diaries for 5 days (120 hours) post chemotherapy (up to 6 cycles) using a 4-point Likert-type scale and reporting adverse events. 
• Complete response (CR) was defined as no emetic episodes and no use of rescue therapy during the overall phase of all planned chemotherapy.
• Complete control (CC) was defined as no emesis, no rescue therapy, and no more than mild nausea.
• No grade 3-4 adverse events reported.

• CR rates ranged rom 74.4%-82.0% per cycle, and CC ranged from 74.4%-82.0% per cycle (CI 95%).
• More than 90% of patients were emesis free during all cycles (CI 95%).
• No severe nausea was detected. More than 60% of patients were nausea free during all chemotherapy cycles.
• The authors did not report on acute versus delayed chemotherapy-induced nausea and vomiting (CINV).

The triple combination of aprepitant, palonosetron, and dexamethasone enhanced antiemetic protection during the first cycle and the efficacy was sustained for up to six cycles of cisplatin-based highly emeotgenic chemotherapy (HEC) in patients with lung cancer. The majority (84%) of patients were able to complete their planned number of chemotherapy treatment cycles.

• Study limitations include the risk of bias because the study had no control group, no blinding, and no random assignment.
• The measurement and methods were not well described.
• The measurement validity and reliability was questionable.
• Forty patients were lost to attrition by cycle 6.

Patients with advanced stage lung cancer treated with HEC who are given CINV prophylaxis according to accepted guidelines prior to each cycle maintain the benefit from the CINV prophylaxis through all cycles of treatment. Managing the distress caused by CINV may increase overall quality of life and is an important consideration when treating patients with palliative chemotherapy.