Masashi Ishihara

Polaprezinc prevents oral mucositis associated with radiochemotherapy in patients with head and neck cancer

Oral mucositis is frequent but serious adverse event associated with radiotherapy or radiochemotherapy in head and neck cancer severely impairs health‐related quality of life, leading to poor prognosis due to discontinuation of the therapy. Although a number of compounds have been tested for prophylaxis of oral mucositis, few of them are satisfactory. We investigated the effect of polaprezinc (zinc L‐carnosine), a gastric mucosal protective drug, on radiochemotherapy‐induced oral mucositis, pain, xerostomia and taste disturbance in patients with head and neck cancer. Patients were randomly assigned to receive polaprezinc (n = 16) or azulene oral rinse as the control (n = 15). The incidence rates of mucositis, pain, xerostomia and taste disturbance were all markedly lower in polaprezinc group than in control. Moreover, the use of analgesics was significantly (p = 0.003) less frequent and the amount of food intake was significantly (p = 0.002) higher in polaprezinc group than in control. On the other hand, tumor response rate in patients with neoadjuvant radiochemotherapy was not significantly affected by polaprezinc, in which the response rate (complete plus partial response) was 88% for polaprezinc and 92% for control (p = 1.000). Therefore, it is highly assumable that polaprezinc is potentially useful for prevention of oral mucositis and improvement of quality of life without reducing the tumor response.

A Multi-institutional Study Analyzing Effect of Prophylactic Medication for Prevention of Opioid-induced Gastrointestinal Dysfunction

Objectives:The aim of this study was to evaluate the effectiveness of prophylactic treatment with laxatives and antiemetics on the incidence of gastrointestinal adverse reactions such as constipation, nausea and vomiting in cancer patients who received oral opioid analgesics for the first time. Methods:A multi-institutional retrospective study was carried out, in which 619 eligible hospitalized patients receiving oral opioid analgesics for cancer pain were enrolled from 35 medical institutions. The primary endpoint was the incidence of opioid-induced side effects in patients receiving prophylactic medication. Odds ratios of the incidence of adverse reactions in the absence or presence of premedication obtained from several institutions were subjected to a meta-analysis. Results:Among 619 patients, the incidence of constipation was significantly lower in patients receiving laxatives, including magnesium oxide, as premedication than in those without them (34% vs. 55%, odds ratio=0.432, 95% confidence interval=0.300-0.622, P<0.001). However, the incidence of nausea or vomiting was similar regardless of prophylactic medication with dopamine D2 blockers. The results of the meta-analysis revealed that prophylactic laxatives significantly reduced the incidence of constipation (overall odds ratio=0.469, 95% confidence interval=0.231-0.955, P=0.037), whereas dopamine D2 blockers were not effective in preventing opioid-induced nausea or vomiting. Discussion:We showed evidence for the effectiveness of premedication with laxatives for prevention of opioid-induced constipation. However, premedication with dopamine D2 blockers was not sufficient to prevent nausea or vomiting.

Pharmacists contribute to the improved efficiency of medical practices in the outpatient cancer chemotherapy clinic

RATIONALE, AIMS AND OBJECTIVES Outpatient cancer chemotherapy is increasing with the development of anticancer agents, and roles of medical staff are becoming more and more important in cancer chemotherapy. We showed here roles of pharmacists with experience in oncology and evaluated outcomes of their activities in medical practices in cancer chemotherapy clinic. METHODS Two pharmacists were newly assigned to the outpatient cancer chemotherapy clinic, where they were in charge of verification of prescription orders, mixing of anticancer injections, monitoring adverse drug reactions, implementation of supportive care and provision of information about cancer chemotherapy to medical staff and patients. The number of patients, amounts of mixing of anticancer injections and hospital revenue were compared before and after assignment of pharmacists. Management of chemotherapy-induced nausea and vomiting in breast cancer patients receiving the combination chemotherapy with anthracycline and cyclophosphamide were also compared. RESULTS Pharmacists spent 75 hours per month in patient education and adverse drug reactions monitoring, which led to the reduction of the workload of physicians. As a consequence, the number of outpatients and the resultant hospital revenue markedly increased. In addition, facilitation of proper use of anti-emetic drugs led to the improved control of chemotherapy-induced nausea with reducing the cost for anti-emesis by 16%. CONCLUSIONS Pharmacists contributed to the improved efficiency of medical practices.

Pharmaceutical interventions facilitate premedication and prevent opioid-induced constipation and emesis in cancer patients

BackgroundOpioid analgesics possess a number of side effects, among which constipation and nausea/vomiting occur most frequently. Although pretreatment with laxatives and antiemetics for the prophylaxis of opioid-induced constipation and nausea/vomiting, respectively, is recommended, such side effects are still a matter of concern in clinical setting.MethodsWe first surveyed the prevalence of premedication in 83 cancer patients who took opioid analgesics and the incidence of such side effects. Subsequently, intervention was carried out to promote premedication, and the effectiveness of the intervention was evaluated in 107 patients.ResultsProphylactic treatment with laxatives and antiemetics were conducted in 57% and 52%, respectively. The most frequently prescribed laxatives and antiemetics were magnesium oxide in combination with pantethine, a mild stimulant laxative, and prochlorperazine, respectively. The lack of premedication increased the risk of constipation (odds ratio, 5.25; 95% confidence intervals, 1.93–14.31; p = 0.001) and vomiting (4.67, 1.04–21.04; p = 0.045). Intervention such as provision of drug information to physicians, verification of prescription orders, and instructions to patients increased the rates of prophylactic medications to 93% (p < 0.001) for laxatives and 81% (p < 0.001) for antiemetics. The incidence of side effects was lowered from 36% to 9% (p < 0.001) for constipation, from 28% to 17% for nausea (p = 0.077), and from 16% to 4% for vomiting (p = 0.0085).ConclusionIntervention to promote prophylactic medication was highly effective in reducing the risk of opioid-induced constipation and nausea/vomiting.

Antacid attenuates the laxative action of magnesia in cancer patients receiving opioid analgesic

This study was designed to investigate pharmacological interaction between magnesium laxative and antacid in patients receiving opioid analgesic.

Prophylactic Effect of Polaprezinc, a Zinc-L-carnosine, Against Chemotherapy-induced Oral Mucositis in Pediatric Patients Undergoing Autologous Stem Cell Transplantation

Background/Aim: Polaprezinc suspension in sodium alginate (PZ-AG) reduces the incidence and severity of oral mucositis in adult patients receiving radiotherapy or high-dose chemotherapy. In the present study, the prophylactic effect of PZ-AG against oral mucositis was assessed in pediatric patients with hematological malignancies receiving high-dose chemotherapy followed by hematopoietic stem cell transplantation (HSCT). Patients and Methods: Data of 16 children who underwent HSCT during a period between January 2010 and December 2017 were obtained from medical records and they were retrospectively analyzed. Oral mucositis was evaluated by the WHO scale. Results: Six (37.5%) of 16 children refused to take PZ-AG in a preliminary assessment and they were pretreated with azulene gargle. The remaining 10 (62.5%) patients were pretreated with PZ-AG for prevention of oral mucositis. Grade≥ 3 oral mucositis occurred in 5 (83.3%) of 6 patients receiving azulene gargle, but in 2 (20%) patients who took PZ-AG (p=0.035). The prevalence for the use of opioid analgesics was also significantly lower (30% vs. 100%, p=0.011), while the average duration of total parenteral nutrition use was significantly shorter (11.1 days vs. 24.3 days, p=0.016), in PZ-AG group than in azulene group. On the other hand, PZ-AG had no significant influence on the incidence of other adverse events, mean time to engraftment, or overall survival. Conclusion: PZ-AG was found to be highly effective in preventing oral mucositis in pediatric patients with hematological malignancies receiving high-dose chemotherapy followed by HSCT, as in adult patients.

Control of Constipation in Patients Receiving CHOP or CHOP-Like Chemotherapy Regimens for Non-Hodgkin’s Lymphoma

Management of constipation in patients receiving cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) or CHOP-like chemotherapy regimens is important for prevention of paralytic ileus. We reported earlier that the laxative action of magnesium oxide is reversed by the concomitant use of antacids in cancer patients receiving opioid analgesics. Here, we assessed the prevalence of prophylactic laxative medication for the control of constipation in patients receiving CHOP or CHOP-like regimens for non-Hodgkins lymphoma. Data obtained from 211 eligible patients were retrospectively analyzed. Almost all patients (99%) received anti-ulcer agents such as proton pump inhibitors and H2 receptor antagonists for the prophylaxis of gastric disorders associated with prednisolone. Prophylactic laxatives were prescribed in 86 patients (40.8%), in which magnesium oxide was used most predominantly (88.4%). However, magnesium oxide at doses of ≦2000 mg/d was not effective for prevention of constipation, although the compound totally inhibited the incidence of constipation at doses higher than 2000 mg/d. Therefore, it is important to avoid negative drug interaction between magnesium oxide and antacids in patients receiving CHOP chemotherapy.

Comparison of the Control of Nausea and Vomiting among Several Moderately Emetic-Risk Chemotherapy Regimens

Background: Different antiemetic medications with or without aprepitant are recommended for moderately emetic-risk chemotherapy (MEC) depending on the emetic potential of chemotherapy agents, although the criterion for the use of aprepitant is still unclear. The present study was designed to compare the control of chemotherapy-induced nausea and vomiting (CINV) among several MEC regimens used in the outpatient chemotherapy setting. Materials and Methods: A single center prospective observational study was carried out in 326 patients who received 2,061 chemotherapy cycles from January 2013 to December 2014. Antiemetic medication consisting of two-drug combination of granisetron (day 1) and dexamethasone (days 1-3) was carried out in 87.6% of patients receiving the first chemotherapy cycle. The checklist for CINV was provided to all patients, and the control of CINV was evaluated on the next visit based on the checklist. Complete inhibition of nausea and vomiting during acute and delayed periods were compared among MEC regimens. Results: Two hundred and one patients received the first cycle of chemotherapy, in which the rates of complete inhibition of nausea and vomiting were 87.6% and 95.5%, respectively, during acute period, and 68.2% and 92.0%, respectively, during delayed period. There were no significant differences in the control of CINV among oxaliplatin, carboplatin and irinotecan, except for the cyclophosphamide-base regimen. Conclusions: Two-drug antiemetic medication of 5-HT3 receptor antagonist and dexamethasone was sufficiently effective for prevention of CINV in most MEC regimens.