[Efficacy and Safety of Trastuzumab Biosimilars in Combination with Pertuzumab].

Although trastuzumab biosimilars have been approved based on clinical studies on their use as monotherapy or in combination with chemotherapy, clinical studies on their combination with pertuzumab are lacking. Data on the efficacy and safety of this combination are scarce. We evaluated the efficacy and safety of trastuzumab biosimilars in combination with pertuzumab. Progression-free survival was 10.5 months(95% confidence interval[CI]: 3.3-16.3)for a reference biological product and 8.7 months(2.1-not applicable)for biosimilars with a hazard ratio of 0.96(95%CI: 0.29-3.13, p=0.94); however, no statistically significant difference was observed. The incidence of adverse events was not significantly different between the reference biological product and biosimilars, and no increase was observed for any adverse events after switching to the biosimilars. The results of this study verify that a combination of trastuzumab biosimilars with pertuzumab is sufficiently effective and safe in clinical practice.

[Evaluation of the Usefulness of Pharmaceutical Outpatient Clinic for Gastric Cancer Patients Receiving Capecitabine plus Oxaliplatin as Postoperative Adjuvant Chemotherapy].

Capecitabine plus oxaliplatin(CapeOX)is widely used as postoperative adjuvant chemotherapy for gastric cancer. The CapeOX regimen often causes digestive symptoms, such as nausea and vomiting under postoperative conditions, and oxaliplatin- induced neurological symptoms, for which supportive intervention is needed. The pharmaceutical outpatient clinic of Jichi Medical University provides pharmaceutical intervention for cancer patients. This study evaluated the usefulness of the pharmaceutical outpatient clinic for gastric cancer patients receiving postoperative adjuvant chemotherapy. The primary endpoint was defined as the effect of the number of outpatient pharmacist interventions on the relative dose intensity of the CapeOX regimen. The secondary endpoint was the correlation between the number of outpatient pharmacist interventions and the worst grade of each side effect. It was observed that patients who received at least 5 outpatient pharmacist interventions had significantly higher dose intensities(p=0.019). Outpatient pharmaceutical interventions were associated with the reduction of side effect symptoms that could be managed with preventive and supportive care. These results showed that continuous intervention by outpatient pharmacists contribute to the optimization of dose intensity and reduction of side effects in gastric cancer patients receiving CapeOX as postoperative adjuvant chemotherapy.

[Assessment of Efficacy and Adverse Effects of Trastuzumab Biosimilar in Gastric Cancer].

The postmarketing assessment of biosimilars is important because posttranslational modification by glycosylation is altered by the manufacturing process. A retrospective study of 15 patients with gastric cancer receiving a combination anticancer therapy with trastuzumab was performed. The most common concurrent regimen was the S-1 and oxaliplatin combination; efficacy and adverse events were assessed in this group. There was no statistically significant difference in progression-free survival between patients receiving the reference formulation and patients receiving its biosimilar. The adverse events detected were similar in both groups. In the 6 patients who switched from the reference trastuzumab to its biosimilar, adverse events did not differ before and after the switch. This small-scale retrospective study found no differences in efficacy or adverse events between the reference trastuzumab and its biosimilar.

[Examination of Fever Risk Factors after Prophylaxis with G-CSF].

Febrile neutropenia is a serious adverse drugreaction to cancer chemotherapy. Prophylactic administration of granulocyte colony-stimulatingfactor (G-CSF)is recommended in patients who require cancer chemotherapy associated with a risk of febrile neutropenia or intense treatment. However, we had patients who developed fever after prophylactic administration of G-CSF. This study investigated the risk factors of fever after prophylactic administration of G-CSF. The subjects were patients who underwent preoperative chemotherapy with docetaxel, cisplatin, and 5-fluorouracil for esophageal cancer and prophylactic administration of G-CSF. Medical charts were retrospectively reviewed for age, sex, date of G-CSF administration, presence or absence of fever after G-CSF administration, Multinational Association for Supportive Care in Cancer(MASCC) risk index score at the time of G-CSF administration, and blood counts at the time of G-CSF administration. The MASCC risk index score(21[17-21]vs 20[19-21])and neutrophil count at the time of G-CSF administration were significantly higher in the non-fever group than in the fever group. Neither factor was an independent risk factor in the multivariate analysis. However, we considered that evaluation at the time of G-CSF administration is useful for early symptomatic treatment of febrile neutropenia.

[A Retrospective Investigation of Lacrimation in Patients Treated with S-1].

Lacrimation is among the typical adverse drug reactions associated with S-1 treatment. However, lacrimation frequencies differ between reports, and a clear consensus regarding reaction times, risk factors, and symptomatic treatment for lacrimation is lacking. We retrospectively investigated the reaction times, risk factors, and outcomes of symptomatic treatment for lacrimation in 202 patients treated with S-1. The median estimated creatinine clearance noted upon initiation of cancer treatment was 75.8mL/min. The median of the relative treatment intensity was 87.1%, while the incidence of lacrimation was 26.7%. The median cumulative dose of S-1 before the onset of lacrimation was 23,520 mg in all patients, and 5,050 mg in those who developed lacrimation. Of the patients who developed lacrimation, 40.7% developed this symptom within 2 months after starting S-1 treatment. There were no apparent risk factors. The most frequently employed symptomatic treatment was a physiological saline ophthalmic solution provided as a hospital preparation. After treatment with this ophthalmic solution, 29.4% of the affected patients showed improvement and 70.6% showed no change; none however, experienced worsening of symptoms. These results suggest that clinicians should assess the presence of lacrimation after starting treatment with S-1. Symptomatic treatment with an ophthalmic solution that does not have a tear retention capacity may be useful in patients who have developed lacrimation.