Multi-Institutional Joint Study on Adverse Events of Original and Generic Gemcitabine Drugs (Gemzar® vs. Gemcitabine Sandoz) Using Propensity Score Matching / 医薬品情報学

Objective: The use of generic drugs is promoted to reduce medical costs and copayments. However, tumor agents are expensive and generic drugs are not widelyused. Thus, it is necessaryto evaluate the safetyof generic drugs in more detail. We compared the incidence of adverse events between the original drug (Gemzar®: GEM) and generic drug (Gemcitabine [Sandoz]: GE-GEM) using propensityscore (PS) matching.Methods: We investigated adverse events in patients who received one course of GEM or GE-GEM. The patient background (age,sex, BSA, cancer type, stage, metastasis, surgical history, and radiotherapy) and administration status (administration route and RDI) were used to calculate the PS.Results: Among all patients (GEM: 51, GE-GEM: 54), a significantlygreater number in the GE-GEM group had cancer metastasis. On comparison of adverse events, there were significantlymore cases of vascular pain (p＜0.05) in the GEM group, and manycases of nausea (p＝0.08) and rash (p＝0.08). Fortypatients in each group were extracted byPS matching. There were no significant differences in the patient background between the groups, and on comparison of adverse events, the two groups did not significantly differ.Conclusion: Our studysuggested that there is no difference in side effects between Gemzar® and gemcitabine [Sandoz]. To compare the incidence of adverse events, it is useful to use PS matching in clinical practice.

An open-label phase 1 dose-escalation clinical trial of a single intravenous administration of gemcitabine in dogs with advanced solid tumors.

BACKGROUND: A broad range of gemcitabine dosages have been used in dogs. HYPOTHESIS/OBJECTIVES: To determine maximally tolerated dose (MTD), dose-limiting toxicity (DLT), and preliminary antitumor activity of intravenous administration of gemcitabine in dogs with advanced solid tumors. ANIMALS: Twenty-two client-owned dogs. METHODS: Dogs with advanced cancer were prospectively enrolled in an open-label Phase 1 study of gemcitabine. Gemcitabine was administered as a 30-minute intravenous bolus starting at 800 mg/m(2), using escalation of 50 mg/m(2) increments with 3 dogs per dose level. MTD was established based on the number of dogs experiencing DLT assessed after 1 cycle. Treatment continued until disease progression or unacceptable toxicosis. Additional dogs were enrolled at MTD to better characterize tolerability, and to assess the extent and duration of gemcitabine excretion. RESULTS: Twenty-two dogs were treated at 4 dose levels, ranging from 800 to 950 mg/m(2). Neutropenia was identified as DLT. MTD was 900 mg/m(2). DLT consisting of grade 4 febrile neutropenia was observed at 950 mg/m(2) in 2 dogs. There were no nonhematologic DLTs. Twenty dogs received multiple doses, and none had evidence of severe toxicosis from any of their subsequent treatments. At 900 mg/m(2), 2 complete and 5 partial responses were observed in dogs with measurable tumors. The amount of gemcitabine excreted in urine decreased over time, and was undetectable after the first 24 hours. CONCLUSIONS AND CLINICAL IMPORTANCE: The recommended dose of gemcitabine for future Phase 2 studies is weekly 900 mg/m(2). In chemotherapy-naïve dogs with advanced solid tumor this dose level merits further evaluation.

Preventive and Therapeutic Effect of Kanglaite Injection on Rat Acute Nephrotox icity Induced by Cisplatin and Gemzar / 中药新药与临床药理

Objective To observe the preventive and therapeutic effect of Ka ng laite Injection (KI) on acute nephrotoxicity in rats induced by cisplatin (DDP) and gemzar.Methods Forty SD rats, male and female in a half, were randomized in to normal control group, KI group, DDP+ Gemzar group and KI+ DDP+ Gemzar gro up, 5 male and 5 female in each group. The KI+ DDP+ Gemzar group were given K I 10 mL/kg first,DDP injection 6 mg/kg 2 hours later and Gemzar injection 90 mg/ kg 4 hours later. After treatment, acute nephrotoxicity was observed.Results On e week after treatment, all of the rats survived; the body weight of the male an d female rats in group was similar in KI group and in the normal control group, but lower in DDP+ Gemzar group, in particular the male rats, than that in norma l control group. Body weight in KI+ DDP+ Gemzar group was lower than that in the normal control group but higher than that in DDP+ Gemzar group.The serum le vels of biochemical parameters were similar in KI group and the normal control g roup; serum levels of total protein (TP) and albumin(ALB) were markedly lower bu t those of blood urea nitrogen (BUN) and creatine (CRE) higher in DDP+ Gemzar g roup than those in the normal control group; the above indexes were improved in KI+ DDP+ Gemzar group as compared with those in DDP+ Gemzar group and arrive to the normal level.Conclusion KI has preventive and therapeutic effect on acu te nephrotoxicity in rats induced by DDP and Gemzar.

Study of Kanglaite Injection Combined with Chemotherapeutic Drugs in Inhibiting the Growth of Transplanted Human Lung Cancer A549 in Nude Mice / 中药新药与临床药理

Objective To observe the attenuated effect of Kanglaite Injecti on (KI) combined with chemotherapeutic drugs on transplanted human lung cancer A54 9 in nude mice. Methods Ninety- six nude mice were transplanted subcutaneousl y with human lung cancer A549; 7 days later, the mice were randomized into 16 gr oups(n=6) and were given antitumor drugs according the regimen. Other 12 normal mice were used as controls. KI groups were given KI 1.25, 2.5 and 5.0 g/kg respe ctively and were administered (iv) continuously for 10 times on 7th day of trans plantation; cisplatin (DDP, 1.5 mg/mg or 3 mg/kg) and Gemzar (30 mg/kg or 60 mg/ kg) were given one dose by intraperitoneal injection on 10th day of transplantat ion; Gemzar was given again 4h after medication of DDP. Taxotere (25 mg/kg) was given one dose by intraperitoneal injection on 7th day of transplantation. The m ice were killed to examine the body weight, tumor weight and tumor- inhibiting rate. Results KI 1.25, 2.5 and 5.0 g/kg respectively combined with DDP 3mg/kg and Gemzar 60 mg/kg had a better inhibitory effect on the growth of human lung c ancer A549 than KI, DDP and Gemzar alone. KI in three doses respectively combine d with DDP 1.5 mg/kg and Gemzar 30 mg/kg not only had a better inhibitory effect than those of KI, DDP and Gemzar alone, but also promoted the antitumor actions . The tumor- inhibitory rate of KI in three doses respectively combined with Ta xotere (25 mg/kg) was higher than KI and Taxotere alone. Conclusion KI combine d with DDP and Gemzar or with Taxotere can shorten the tumor mass and has tumor - inhibitory and attenuated effect.