[Trastuzumab in combination with chemotherapy versus chemotherapy alone for first-line treatment of HER2-positive advanced gastric or gastroesophageal junction cancer: a Phase III, multi-center, randomized controlled trial, Chinese subreport].

OBJECTIVE: To evaluate the efficacy and safety of trastuzumab in combination with chemotherapy versus chemotherapy alone in the first-line treatment of HER-2-positive advanced gastric or gastro-oesophageal junction cancer. METHODS: Fifteen Chinese research centers are involved in the BO18255 (ToGA) study. Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumor showed overexpression of HER-2 protein by immunohistochemistry +++ or FISH-positive. Patients were randomly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine or 5-FU plus cisplatin or chemotherapy in combination with intravenous trastuzumab. The primary endpoint was overall survival. RESULTS: Eighty-five Chinese patients were enrolled in this study, of whom 84 were included in the primary analysis: trastuzumab plus chemotherapy (FP/H) (n = 36) and chemotherapy alone (FP)(n = 48). The median follow-up was 15.2 months in the FP/H group and 14.2 months in the FP group. The median survival time was 12.6 months in the FP/H group compared with 9.7 months in the FP group [hazard ratio 0.72, 95%CI (0.40; 1.29)]. Grade 3/4 adverse events were higher in the FP/H(63.9%)than FP (47.9%) groups, including neutropenia, vomiting and nausea. Two mild cardiac adverse events occurred in the FP/H group. Severe adverse events occurred in 3 cases of both two groups, respectively. CONCLUSIONS: Addition of trastuzumab to chemotherapy is well tolerated and shows improved survival in Chinese patients with advanced gastric or gastro-oesophageal junction cancer. These results are consistent with the results of ToGA whole population trial. Trastuzumab in combination with chemotherapy can be considered as a new option for patients with HER-2-positive advanced gastric or gastro-oesophageal junction cancer.

Lack of influence of XRCC1 and XPD gene polymorphisms on outcome of platinum-based chemotherapy for advanced non small cell lung cancers.

PURPOSE: Genetic polymorphisms of DNA repair genes are associated with differential enzyme activity and may help explain interindividual differences in response rates after platinum-based chemotherapy for non small cell lung cancers (NSCLCs). This study was conducted to assess relationships between X-ray repair cross complementing group1 (XRCC1) and xeroderma pigmentosum group D (XPD) genetic polymorphisms and outcome in NSCLC patients. METHODS: From March 1, 2005 to December 31, 2008, the polymerase chain reaction-restriction fragment length polymorphism method was applied to evaluate genetic polymorphisms of the XRCC1 codon399 (Arg/Gln) and XPD codon751 (Lys/Gln) DNA repair genes in 108 patients with stage IIIB and IV NSCLCs treated with platinum-based chemotherapy in the Department of Chemotherapy of Jiangsu Cancer Hospital and Research Institute. RESULTS: Among the assessed NSCLC patients, the overall response rate of chemotherapy was 21.6%. No association was found with either of the genetic polymorphisms, although the XRCC1 399Arg/Arg genotype was associated with a non-significant higher median survival time (29 months versus 21 months for the Arg/Gln genotype and 15 months for the Gln/Gln genotype, P= 0.09). CONCLUSION: Our results suggested no influence of the XRCC1 codon399 (Arg/Gln) and XPD codon751 (Lys/Gln) genetic polymorphisms on treatment response and survival in advanced NSCLC patients with platinum-based chemotherapy.

[Tropisetron hydrochloride in preventing and treating chemotherapy-induced nausea and vomiting: a phase II, randomized, multicenter, double-blinded, comparative clinical trial].

BACKGROUND & OBJECTIVE: Tropisetron hydrochloride (Navoban), as a highly selective 5-hydroxytryptamine 3 (5-HT3) receptor antagonist, has been widely used in preventing and treating chemotherapy-induced nausea and vomiting for many years. This study was to evaluate the efficacy and safety of homemade tropisetron hydrochloride in preventing and treating cisplatin-based chemotherapy-induced nausea and vomiting. METHODS: A randomized, double-blinded, multicenter, comparative trial was conducted in cancer patients receiving cisplatin-based chemotherapy. All patients were assigned to group A-B or B-A randomly, and took homemade tropisetron hydrochloride and Navoban (positive control agent) to treat chemotherapy-induced nausea and vomiting. RESULTS: A total of 118 patients were enrolled: 60 in group A-B and 58 in group B-A. There was no difference in the efficacy of relieving acute vomiting between homemade tropisetron hydrochloride and Navoban (P>0.05). The inhibition rates of nausea and vomiting were 28.59% and 52.61% respectively in group A-B, while 29.21% and 51.94% in group B-A (P>0.05). In addition, quality of life (QOL) showed no significant difference between the 2 groups at Days 3, 6, 10, and 21 (P>0.05). Besides, the occurrence rate of adverse events, such as constipation, abdominal distention, vertigo, headache and fatigue, was 27.97% in group A-B and 22.03% in group B-A (P>0.05). CONCLUSION: Homemade tropisetron hydrochloride injection has both reliable efficacy and safety in preventing and treating cisplatin-induced acute or chronic nausea and vomiting; it is comparable with Navoban on many aspects, such as long action time, less adverse effects and improved QOL.

[Phase II clinical trial of home-produced Nedaplatin in treating advanced esophageal carcinoma].

BACKGROUND & OBJECTIVE: Nedaplatin is a second-generation anticancer drug containing organic platinum. Clinical researches in overseas showed that Nedaplatin is an anticancer drug with broad spectrum and high efficiency, especially in treating esophageal carcinoma. But the therapeutic efficacy and toxicity of home-produced Nedaplatin in China are unclear. This study was to evaluate the efficacy of home-produced Nedaplatin in China on esophageal carcinoma, and observe its toxicity. METHODS: A multi-center, phase II, prospective clinical trial was conducted. Naive patients with esophageal carcinoma were enrolled and randomized into trial group and control group. The patients in trial group were treated with home-produced Nedaplatin plus 5-fluorouracil (5-FU); the patients in control group were treated with cisplatin (DDP) plus 5-FU. RESULTS: A total of 52 patients were enrolled: 30 in trial group, and 22 in control group. For trial group, therapeutic efficacy was evaluable in 27 cases, and toxicity was evaluable in all cases; for control group, therapeutic efficacy and toxicity were evaluable in all cases. The response rate was significantly higher in trial group than in control group (29.62% vs. 22.72%, P<0.05). The complete remission (CR) rates were 18.51% in trial group and 4.55% in control group. When considering myelosuppression, the occurrence rate of anemia was similar in the 2 groups; but the occurrence rates of neutropenia and thrombocytopenia were higher in trial group than in control group, especially for grade III-IV thrombocytopenia (20.68% vs. 0%, P<0.01). The occurrence rate of gastrointestinal reaction was lower in trial group than in control group. There were no significant differences in hepatotoxicity, renal toxicity, heart toxicity, peripheral nerve toxicity, and alopecia between the 2 groups. CONCLUSIONS: Nedaplatin is an effective platinum drug for esophageal carcinoma. The treatment efficacy of Nedaplatin plus 5-FU regimen is better than that of DDP plus 5-FU regimen. It has a good clinical tolerance. The main toxicity is myelosuppression, and thrombocytopenia is predominant.

[Chronomodulated chemotherapy of oxaliplatin, 5-fluorouracil and folinic acid for advanced gastric cancer].

OBJECTIVE: The combination of oxaliplatin (L-OHP), 5-fluorouracil (5-Fu) and folinic acid (FA), being one of the effective regimens for advanced gastric cancer, is used in form of chronomodulated chemotherapy for advanced gastric cancer to investigate its efficacy and safety. METHODS: Twenty-six patients received a 4-day chronomodulated infusion of L-OHP, 5-Fu and FA. L-OHP (25 mg.m(-2).d(-1)) infused from 10:00 am to 22:00 pm, and followed by 5-Fu (600 mg.m(-2).d(-1)) and FA (300 mg.m(-2).d(-1)) from 22:00 pm to 10:00 am for 4 days using a multichannel programmable pump, every 2 weeks as an cycle for at least 2 cycles. RESULTS: Twenty-six patients with previously untreated advanced gastric cancer were eligible. Two complete and 13 partial remissions were observed with an overall response rate of 57.7%. Stable disease was observed in 6 patients (23.1%) and progressive disease in five (19.2%). Four of these patients underwent surgery. The median remission time was 3.5 months and time to tumor progression (TTP) was 4.5 months. The median overall survival time was 8 months. A total of 80 cycles were given without any grade 4 toxicity observed, but grade 3 thrombocytopenia (1.3%) and mucositis (1.3%) in one patient, two grade 3 neutropenia (2.5%) and nausea/vomiting (2.5%) in 2. CONCLUSION: Chronomodulated intravenous chemotherapy of oxaliplatin, 5-fluorouracil and folinic acid is effective and safe in the treatment of advanced gastric cancer.

[Oxaliplatin in combination with LV5FU2 for advanced/metastatic gastric cancer-a multicenter study].

OBJECTIVE: To evaluate the effects and safety of OXA-LV5FU2 regimen for patients with advanced/metastatic gastric cancer. METHODS: OXA 100 mg/m(2) i.v. 2hr d1, LV200 mg/m(2) i.v. 2hr followed by 5-Fu 400 mg/m(2) i.v. bolus and 5-Fu 600 mg/m(2) i.v. 22hr d1, 2 were given, and repeated every 2 weeks. Efficacy was evaluated at 4 cycles (8 weeks). RESULTS: Forty three patients have been entered into the study. Patients with primary tumor resected or non-resected were 17 and 26. The evaluable lesions were 26 primary lesions, 22 lymph node metastases, 12 liver metastases, 1 pancreas metastasis and 2 soft tissue metastases. Forty patients were evaluable for clinical response. Four patients achieved CR (10.0%), 13 PR (32.5%), ORR 42.5% (95% CI 27.2 - 57.8), 17 SD (42.5%) and 6 PD (15.0%). Overall response rate (ORR) for chemotherapy naive (1(st) line) and pretreated (2(nd) line) patients were 50.0% (14/28) and 25.0% (3/12), respectively. Median time to progress (mTTP) was 5 months and median overall survival (mOS) was 8 months. Forty-three patients were evaluable for toxicity, with Grade 3, 4 WHO toxicity of neutropenia in 7 patients (16.3%), thrombocytopenia in 3 patients (7.0%), nausea/vomiting in 1 patient (2.3%). There were no Grade 3, 4 peripheral neuropathy toxicity or any deaths during treatment. CONCLUSION: OXA-LV5FU2 is a high response regimen for advanced gastric cancer with mild toxicity, which can be practiced safely.

[Phase II clinical trial of nedaplatin in advanced non-small cell lung cancer].

BACKGROUND & OBJECTIVE: The aim of this study was to observe the efficacy and the side effects of nedaplatin in treatment of non-small cell lung cancer (NSCLC). METHODS: This is a multi-center phase II clinical trial. The previously chemotherapy treated patients with NSCLC were administrated nedaplatin alone. Nedaplatin was given at 100 mg/m2, i.v., repeated every 3 weeks. The chemonaive patients with NSCLC were randomized to two groups. The combination trial group was given with nedaplatin + vindesine regimen, and the combination control group with cisplatin + vindesine. RESULTS: Of 138 patients, 16 were in the nedaplatin single drug group; 60 were in the combination trial group; and 62 were in the combination control group. All of the 16 cases in the single drug group, which were treated with platinum previously, achieved 12.5% of response rate. And the combination trial group and control group had a very similar response rate, which were 26.7% versus 25.8%, respectively. The incidence rates of neutropenia and anemia were similar in the two groups. But the incidence rate of thrombocytopenia was higher in the trial group than that in the control group. Nedaplatin has a possibility to result in mild nausea/vomiting. CONCLUSION: Nedaplatin is an effective platinum drug in the treatment of NSCLC, not only for no previously chemotherapy patients, but also for those patients resistant to cisplatin/carboplatin. Nedaplatin has a good clinical tolerance. And the main adverse reaction was myelosuppression, especially thrombocytopenia.