Dronabinol in combination with prochlorperazine
Lane et al12 conducted a multicentered, randomized, parallel group, double-blind trial that enrolled 62 patients. All the patients had previously received chemotherapy and antiemetics. Patients were eligible for the trial if they were receiving any chemotherapy agents except high-dose cisplatin (>60 mg/m2). The most common chemotherapy agents were doxorubicin and cyclophosphamide (n=26), 5-fluorouracil (n=14), vincristine (n=13), and etoposide (n=10). Two or three drug chemotherapy regimens were given to 79% of patients. Patients were randomized to one of three arms: dronabinol 10 mg PO every 6 hours with placebo (n=21), prochlorperazine 10 mg PO every 6 hours with placebo (n=21), or dronabinol 10 mg PO every 6 hours with prochlorperazine 10 mg PO every 6 hours (n=20). Patients started the prescribed antiemetic 24 hours prior to starting chemotherapy and continued it until 24 hours after the last dose of chemotherapy.
The overall complete response rate was defined as no episodes of nausea or vomiting and occurred in 41% in the dronabinol group and 30% in the prochlorperazine group (P<0.0001).12 No complaints of nausea or vomiting occurred in 41% in the dronabinol group, 30% in the prochlorperazine group, and 47% in the combination group. Two or fewer nausea or vomiting episodes occurred in 71%, 45%, and 65% in the dronabinol, prochlorperazine, and combination groups, respectively. The median duration per episode of nausea or vomiting was 2 minutes in the combination group compared to 5 minutes in the dronabinol and prochlorperazine groups (P<0.001). In addition, the severity of the nausea was less in the combination group versus the dronabinol and prochlorperazine groups (P<0.001). The duration per episode of nausea or vomiting in the dronabinol group was 2 and 10 minutes versus 4 and 15 minutes in the prochlorperazine group. However, the total duration of nausea and vomiting episodes did not differ between the three treatment groups. Eleven patients reported anticipatory nausea (30% in dronabinol group, 0% in the prochlorperazine group, and 26% in the combination group).
Thirty-four patients reported adverse drug effects in the dronabinol (n=16), prochlorperazine (n=7), and combination (n=11) groups.12 The difference of reported adverse drug effects was statistically significant between the dronabinol and prochlorperazine groups (P<0.01). Most of the adverse drug effects reported were mild to moderate. The most common type of adverse effects reported were neuropsychotropic, seen in a total of 48% of patients. The incidence of neuropsychotropic adverse drug effects that was reported in the dronabinol and prochlorperazine groups was 62% versus 29% (P=0.06). In the combination group, it was reported in 55% of patients. Overall, 14 patients withdrew (ten patients in dronabinol group and four in combination group) due to adverse drug effects, with neuropsychotropic effects being the most common reason and beginning during the prechemotherapy phase.
Indicated dronabinol dosage
Dronabinol is typically prescribed at a dosage of 5 mg PO three or four times daily to control CINV.7On the basis of the patient’s response after each chemotherapy cycle, the dose may be increased or decreased as tolerated. Another option for dosing dronabinol is 5 mg/m2 PO every 1–3 hours prechemotherapy and then every 2–4 hours for a total of 4–6 doses/d. The maximum individual dose is 15 mg/m2.
PATIENT PERSPECTIVES OF DRONABINOL
CB1/CB2 receptor agonists can produce adverse effects in patients, and many of these are likely caused by the activation of central CB1 receptors rather than CB2 or peripheral CB1 receptors.5
In 18 cross-over trials included in the Tramer et al10 meta-analysis, when patients were questioned which antiemetic was preferred, 38%–90% of patients preferred cannabinoids. Four trials compared cannabinoids to placebo. Out of 202 patients, 153 patients preferred cannabinoids versus 27 patients preferring the placebo (NNT =1.6). In ten additional trials comparing cannabinoids to an active control, 371 out of 604 (61%) preferred cannabinoids versus 156 patients (26%) preferring the active control.
In the Rocha et al’s11 meta-analysis, 18 double-blind and cross-over trials (n=1,138) included an analysis of the patient’s preference of cannabinoids, and it resulted in a statistically significant difference in favor of cannabinoids (NNT =1.8, P<0.00001). The cannabinoids included in the different trials included dronabinol, nabilone, and levonantradol compared to the controls of prochlorperazine, chlorpromazine, domperidone, haloperidol, alizapride, metoclopramide, and placebo. A relationship was determined with the control drug that was utilized.
It is suggested that patients prefer the “beneficial” adverse drug effects associated with dronabinol, such as, sedation, sensation of a “high”, and somnolence.10,11 These adverse drug effects might provide relief while receiving chemotherapy.11 Another view is since CINV has such a major impact on the patient’s QoL and can cause such discomfort to the patient, the patients prefer cannabinoids’ adverse drug effects instead of the conventional medications that might be less effective in preventing and relieving the CINV.11