[A randomized controlled trial with methotrexate (MTX), 5-fluorouracil (5-FU) and pirarubicin (THP) vs 5-FU alone in advanced or recurrent gastric carcinoma. Tokai Hokuriku THP Study Group]. Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer. [Clinical study on treatment of mid-late stage gastric carcinoma by composite xiansu capsule combined with chemotherapy]. Controlled evaluation of three drug combination regimens versus fluorouracil alone for the therapy of advanced gastric cancer. North Central Cancer Treatment Group. Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. Randomized controlled trial of the efficacy of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil and uracil/tegafur. Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, double-dummy, randomised, comparative phase III trial. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Quality of life in patients with advanced gastric cancer: a randomized trial comparing docetaxel, cisplatin, 5-FU (TCF) with epirubicin, cisplatin, 5-FU (ECF).
A randomized controlled trial was designed to investigate the therapeutic benefit of a combination chemotherapy consisting of MTX, 5-FU and THP in patients with advanced or recurrent gastric carcinoma. The patients were randomized into two groups; Group A patients (n = 37) underwent our combined chemotherapy, whereas Group B (n = 34) underwent chemotherapy with 5-FU alone as a control. There were no significant differences in various background factors between the groups. The median survival time was roughly 170 days after the randomization for the patients with advanced cancer (n = 26 for Group A and n = 25 for Group B), with no significant difference between the groups. Two long survivors, however, belonged to Group A. The median survival time of 161 days for Group A (n = 11) was longer than that of Group B (84 days, n = 9), but the difference was not statistically significant. The incidence of toxicities (leukopenia in particular) exceeding JCOG grade 3 was significantly higher for Group A, but no morbidity was observed. These results imply that patients with advanced or recurrent gastric carcinoma may benefit from a regimen of MTX, 5-FU and THP. In an attempt to decrease the toxic effects of fluorouracil, doxorubicin, and methotrexate (FAMTX) by reducing the dose of methotrexate from 1500 mg/m2, according to the original regimen, to 1000 mg/m2, the authors designed the modified FAMTX treatment that was evaluated in a prospective Phase II-III randomized trial.
                Patients with advanced gastric cancer were randomized to receive modified FAMTX treatment or supportive measures only (control group). In the middle of the study, the randomization was interrupted because of strong evidence of benefit in terms of tumor reduction and projected survival in the treatment arm receiving chemotherapy. By the end of the study, 30 assessable patients had received chemotherapy and 10 had received supportive treatment.
                The overall response rate was 50% (15 patients); 12 patients (40%) had partial responses and 3 (10%) had complete responses (CR). One patient with extensive peritoneal carcinomatosis attained a CR pathologically documented by laparoscopic examination and peritoneal biopsy. The median overall survival time of the treated group was 9 months, whereas that of the control group was only 3 months (P = 0.001). The median overall survival time of the responders was 16 months, and their median remission duration was 8 months. The regimen was well tolerated, with a very acceptable toxicity profile. There was one toxic death resulting from neutropenia and sepsis in a patient who did not receive adequate leucovorin rescue.
                This regimen appears to prolong survival in patients with advanced gastric cancer, and the reduction of the methotrexate dose does not seem to compromise its efficacy. To assess the effect and mechanism of composite Xiansu Capsule (CXSC) combined with chemotherapy in treating gastric carcinoma of mid-late stage.
                The 61 patients of the test group were treated by CXSC combined with chemotherapy and 30 patients of the control group treated with chemotherapy alone. The effect of treatment and cell mediated immunity of patients were observed.
                The effective rate of the test group and the control group was 32.8% and 13.3% respectively (P < 0.05), the chemotherapy caused toxic reaction occurrence was less in the former than that in the latter group (P < 0.01). The CD3 level of patients in the test group was decreased, and CD4/CD8 level was raised obviously, which suggested that CXSC had immuno-regulating effect on T-cells.
                CXSC could enhance the efficacy and reduce the toxic side-effect of chemotherapy. To regulate the cell mediated immunity of patients is possibly its mechanism. The purpose of this study was to evaluate the therapeutic effectiveness of fluorouracil (5-FU), doxorubicin, and methyl lomustine (CCNU) (FAMe), 5-FU, doxorubicin, and cisplatin (FAP), and FAMe alternating with triazinate (TZT) when compared with a standard therapy of 5-FU alone in patients with advanced gastric cancer.
                Two hundred fifty-two eligible patients selected for study had proven locally unresectable and/or metastatic gastric adenocarcinoma. The majority had nonmeasureable disease. They were randomly assigned to receive one of the three drug combination regimens or to 5-FU alone administered by rapid injection in 5-day course. Survival was the primary study end point.
                None of the three drug combinations showed a significant advantage over 5-FU alone in improved performance score, weight gain, or patient survival. Each of the three combinations was more toxic than 5-FU alone.
                FAMe, FAP, or FAMe alternating with TZT cannot be recommended for the therapy of advanced gastric carcinoma. Therapy of this disease should remain an experimental endeavor. It would seem reasonable to prove the value of any new treatment approach by a randomized comparison to simple therapy with 5-FU alone. The extent to which chemotherapy may relieve tumour-related symptoms, improve quality of life and prolong survival in patients with gastric cancer is not known in spite of the extensive use of this treatment modality. The aim of this study was to estimate any gain in the quantity and quality of life produced by chemotherapy in these patients.
                Between January 1991 and February 1995, 61 patients with gastric cancer were randomized to either chemotherapy in addition to best supportive care or to best supportive care. Chemotherapy was allowed in the latter group if the supportive measures did not lead to palliation. Chemotherapy was the ELF-regimen consisting of 5-fluorouracil, leucovorin and etoposide, or, in elderly patients with poor performance, a 5-fluorouracil/leucovorin regimen (FLv). Quality of life was evaluated with the EORTC-QLQ-C30 instrument.
                More patients in the chemotherapy group (45%, 14/31) had an improved or prolonged high quality of life for a minimum period of 4 months compared to those in the best supportive care group (20%, 6/30, P < 0.05). A similar difference was seen in the treating physician's evaluation of whether the patient was subjectively improved or continued to do well for at least 4 months (17/31, 55% versus 6/30, 20%, P < 0.01). Overall survival was longer in the chemotherapy group (median 8 vs. 5 months) although the difference was not statistically significant (P = 0.12). After corrections for imbalances in pretreatment characteristics, chemotherapy treatment was, however, associated with a survival benefit (P = 0.003). Also, the quality-adjusted survival time and time to disease progression were longer for patients randomized to chemotherapy (median 5 vs. 2 months, P = 0.03).
                The results show that chemotherapy can add to both quantity and quality of life in advanced gastric cancer. The number of patients who benefit from treatment is, however, still rather limited. We investigated the efficacy and safety of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil (carmofur, HCFU) and uracil/tegafur (UFT).
                Patients with stage II, III, or IV (Dukes' B, C) colorectal cancer were enrolled and randomly assigned to one of three groups: an immunochemotherapy group (mitomycin C [MMC] + 5-fluorouracil [5-FU] + HCFU + OK-432), a chemotherapy group (MMC + 5-FU + HCFU), and a control group (surgery alone) for those with colon cancer (study 1); and an immunochemotherapy group (MMC + 5-FU + UFT + OK-432), a chemotherapy group (MMC + 5-FU + UFT), and a control group (surgery alone) for those with rectal cancer (study 2).
                A total of 760 patients with colon cancer and 669 patients with rectal cancer were entered into this randomized clinical trial (RCT). The incidence of side-effects was in the order of: immunochemotherapy group > chemotherapy group > control group in both the cohort of patients with colon cancer and the cohort with rectal cancer. In particular, the frequency of leucopenia and skin disorders was significantly higher than control groups. There were no severe adverse events such as death related to the adjuvant therapy. In both the colon cancer and rectal cancer cohorts, no significant difference in the 5-year survival rate and disease-free survival rate was noted among the three groups.
                The results of an RCT demonstrated that the combination of MMC + 5-FU + HCFU + OK-432 for colon cancer and that of MMC + 5-FU + UFT + OK-432 for rectal cancer could not prolong the survival of patients with surgically resected colorectal cancer, but that both combinations were well tolerated as adjuvant therapy. We investigated the efficacy and safety of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil (carmofur, HCFU) and uracil/tegafur (UFT). Palonosetron is a second-generation 5-hydroxytryptamine 3 (5-HT(3))-receptor antagonist that has shown better efficacy than ondansetron and dolasetron in preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy, and similar efficacy to ondansetron in preventing CINV in patients receiving highly emetogenic chemotherapy. In this phase III, multicentre, randomised, double-blind, double-dummy, stratified, parallel-group, active-comparator trial, we assessed the efficacy and safety of palonosetron versus granisetron for chemotherapy-induced nausea and vomiting, both of which were administered with dexamethasone in patients receiving highly emetogenic chemotherapy.
                Between July 5, 2006, and May 31, 2007, 1143 patients with cancer who were receiving highly emetogenic chemotherapy (ie, cisplatin, or an anthracycline and cyclophosphamide combination [AC/EC]) were recruited from 75 institutions in Japan, and randomly assigned to either single-dose palonosetron (0.75 mg), or granisetron (40 microg/kg) 30 min before chemotherapy on day 1, both with dexamethasone (16 mg intravenously) on day 1 followed by additional doses (8 mg intravenously for patients receiving cisplatin or 4 mg orally for patients receiving AC/EC) on days 2 and 3. A non-deterministic minimisation method with a stochastic-biased coin was applied to the randomisation of patients. Covariates known to effect emetic risk, such as sex, age, and type of highly emetogenic chemotherapy, were used as stratification factors of minimisation to ensure balance between the treatment groups. Primary endpoints were the proportion of patients with a complete response (defined as no emetic episodes and no rescue medication) during the acute phase (0-24 h postchemotherapy; non-inferiority comparison with granisetron) and the proportion of patients with a complete response during the delayed phase (24-120 h postchemotherapy; superiority comparison with granisetron). The non-inferiority margin was predefined in the study protocol as a 10% difference between groups in the proportion of patients with complete response. The palonosetron dose of 0.75 mg was chosen on the basis of two dose-determining trials in Japanese patients. All patients who received study treatment and highly emetogenic chemotherapy were included in the efficacy analyses (modified intention to treat). This trial is registered with ClinicalTrials.gov, number NCT00359567.
                1114 patients were included in the efficacy analyses: 555 patients in the palonosetron group and 559 patients in the granisetron group. 418 of 555 patients (75.3%) in the palonosetron group had complete response during the acute phase compared with 410 of 559 patients (73.3%) in the granisetron group (mean difference 2.9% [95% CI -2.70 to 7.27]). During the delayed phase, 315 of 555 patients (56.8%) had complete response in the palonosetron group compared with 249 of 559 patients (44.5%) in the granisetron group (p<0.0001). The main treatment-related adverse events were constipation (97 of 557 patients [17.4%] in the palonosetron group vs 88 of 562 [15.7%] in the granisetron group) and raised concentrations of serum aminotransferases (aspartate aminotransferase: 24 of 557 [4.3%] vs 34 of 562 [6.0%]; alanine aminotransferase: 16 of 557 [2.9%] vs 33 of 562 [5.9%]); no grade 4 main treatment-related adverse events were reported.
                When administered with dexamethasone before highly emetogenic chemotherapy, palonosetron exerts efficacy against chemotherapy-induced nausea and vomiting which is non-inferior to that of granisetron in the acute phase and better than that of granisetron in the delayed phase, with a comparable safety profile for the two treatments.
                Taiho Pharmaceutical (Tokyo, Japan). Phase 2 studies suggest that the monoclonal antibody rituximab may improve the prognosis of patients with follicular lymphoma (FL) when it is added to chemotherapy. In the current study, 428 patients with untreated, advanced-stage FL were randomly assigned for therapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) alone (n = 205) or CHOP combined with rituximab (R-CHOP) (n = 223). R-CHOP reduced the relative risk for treatment failure by 60% and significantly prolonged the time to treatment failure (P < .001). In addition, a significantly higher overall response rate (96% vs 90%; P = .011) and a prolonged duration of remission (P = .001) were achieved. In spite of a relatively short observation time, these beneficial effects even translated to superior overall survival (P = .016), with 6 deaths in the R-CHOP group compared with 17 deaths in the CHOP group within the first 3 years. The predominant treatment-related adverse effect was myelosuppression. Severe granulocytopenia was more frequently observed after R-CHOP (63% vs 53%; P = .01). However, severe infections were rare and of similar frequency after R-CHOP and CHOP (5% and 7%). Hence, adding rituximab to CHOP significantly improves the outcome for patients with previously untreated advanced-stage FL and does not induce major adverse effects. Health related quality of life (HRQOL) is an important outcome after treatment for upper gastrointestinal carcinoma. This study aimed to compare HRQOL in patients with advanced gastric cancer (GC) receiving either a standard or an experimental treatment.
                Seventy-one patients have been treated in Cancer Institute (Tehran, Iran) with docetaxel, cisplatin, 5 FU (TCF) or epirubicin, cisplatin, 5-FU (ECF) and were followed from Jan 2002 to Jan 2005. End points were response rate, HRQOL and survival. HRQOL was assessed using the EORCT QLQ-C30 at baseline and after the third cycle of chemotherapy.
                The baseline HRQOL scores were comparable between two groups. After treatment improvement was seen in a number of items and domains except for cognitive functioning, and diarrhoea. Pain decreased and physical functioning improved in both groups. However, only the TCF group showed statistically and clinically meaningful improvement in global QOL (P = 0.001). Surgical and pathologic response was better with TCF but there was no difference in survival rate between two groups.
                Docetaxel based treatment (TCF) showed better palliation and improvement of global QOL as compared with epirubicin based treatment (ECF). However, it seems that regardless of treatment offered, effective chemotherapy was the most important factor affecting QOL in these patients.
This review did not provide assured evidence concerning the effectiveness of TCMHs in improving quality of life or rate of remission, alleviating the toxicity or side effects of chemotherapy, or reducing short-term mortality. Limited, weak evidence showed that Huachansu, Aidi, Fufangkushen, and Shenqifuzheng improved leukopenia when used together with chemotherapy; and Huachansu, Aidi, and Fufangkushen were of benefit for adverse events in the digestive system caused by chemotherapy. These TCMHs did not improve the rate of short-term remissions. Large, well designed clinical trials are required urgently before any definite conclusions can be drawn about the value of TCMHs for advanced or late stage gastric cancer.