Combination chemotherapy with paclitaxel, cisplatin and fluorouracil for patients with advanced and metastatic gastric or esophagogastric junction adenocarcinoma: a multicenter prospective study.

OBJECTIVE: To evaluate the efficacy and toxicity of the combination regimen of paclitaxel, cisplatin and 5-FU (PCF) as first-line or second-line therapy in patients with advanced gastric and esophagogastric junction (EGJ) adenocarcinoma in China. METHODS: The patients were treated with paclitaxel 150 mg/m(2) on d1; fractionated cisplatin 15 mg/m(2) and continuous infusion 5-FU 600 mg/(m(2)·d) intravenously on d1-d5 of a 21-d cycle until disease progression or unacceptable toxicities. RESULTS: Seventy-five patients have been enrolled, among which, 41 received PCF regimen as the first-line therapy (group A) and 34 received the regimen as the second-line therapy (group B) with the median age of 59 years old and Karnofsky performance status (KPS) score ≥80. Toxicities were analyzed in all 75 patients. Seventy-one patients were evaluable for efficacy. The median overall survival (mOS) was 12.0 months (95% CI: 7.9-16.2 months) in group A and 7.3 months (95% CI: 4.3-10.3 months) in group B, respectively. The median progression-free survival (mPFS) was 5.7 months (95% CI: 4.1-7.2 months) and 5.0 months (95% CI: 3.1-6.9 months), respectively. The response rate (CR+PR) was 40% (16/40; 95% CI: 24.9-56.7%) in group A and 22.6% (7/31; 95% CI: 9.6-41.1%) in group B. Major grade 3 or 4 adverse events include neutropenia (41.3%), febrile neutropenia (9.3%), nausea/anorexia (10.7%), and vomiting (5.3%). There was no treatment-related death. CONCLUSIONS: The combination chemotherapy with PCF is active and tolerable as first-line and second-line therapy in Chinese patients with advanced gastric and EGJ adenocarcinoma. The response and survival of PCF are same as those of DCF, but the tolerance is much better.

[Irinotecan plus fuorouracil/leucovorin (FOLFIRI) as a second line chemotherapy for refractory or metastatic colorectal cancer].

OBJECTIVE: Irinotecan (CPT-11), a specific inhibitor of topoisomerase I, has been proven to be effective in the treatment of refractory or metastatic colorectal cancer. Furthermore, several first line phase III trials of the combination therapy (FOLFIRI) using CPT-11 and fuorouracil/leucovorin (5-Fu/LV) were reported to have significant improvement in treatment result. Therefore, we designed a multicenter clinical study to observe the overall survival (OS), time to death (TTD), time to progression (TTP), efficacy and safety of FOLFIRI regimen for patients with refractory or metastatic colorectal cancer after first line chemotherapy failure. METHODS: Patients with metastatic or refractory colorectal cancer after first line oxaliplatin-based chemotherapy failure were enrolled into this prospective, one arm and open-labeled multicenter study. Irinotecan 180 mg/m2 was administered biweekly on D1, LV 200 mg/m2 by intravenous infusion in 2 hours before bolus intravenous injection of 5-Fu 400 mg/m2, then followed immediately by intravenous infusion of 5-Fu 2.4 g/m2 in 46 hours. OS, TTD, TTP, response rate (RR) and adverse events were assessed according to RSCIST criteria and NCIC-CTG CTCAE (3.0). RESULTS: Sixty-six patients were valuable for safety assessment and and 61 for efficacy. There was no CR patient in this series. Ten patients had PR, 35 SD (57.4% ) and 16 PD (26.2%) with a response rate of 16.4% (10/61). The median TTP was 5.0 months (1-12 months), median TTD 9.9 months (5-27 months)and median OS 18.2 months (7-33 months). The adverse events including nausea,vomiting, anorexia,diarrhea, leucopenia and cholinergic syndrome were frequent, but usually in I - II degree. The rate of III/IV degree diarrhea and leucopenia was 7.6% and 22.7%, respectively. CONCLUSION: The regimen of irinotecan plus fuorouracil/leucovorin (FOLFIRI) is effective and well-tolerated as a second-line chemotherapy and may prolong the overall survival for the patient with refractory or metastatic colorectal cancer.

[Capecitabine combined with cisplatin as first-line therapy in Chinese patients with advanced gastric carcinoma-a phase II clinical study].

OBJECTIVE: To evaluate the effectiveness and safety of the combination chemotherapy of capecitabine (X) with fractionated administration of cisplatin (C) in Chinese patients with advanced gastric cancer (AGC). METHODS: 141 patients with AGC were enrolled between July 2002 and August 2004. All patients had measurable tumor according to the criteria of RECIST, Karnofsky performance status > or = 60, adequate bone marrow, renal and hepatic functions. Prior radiotherapy or adjuvant chemotherapy was not permitted. Patients received oral administration of capecitabine at a dose of 1000 mg/m(2) twice a day on D1-D14, and intravenous infusion of fractionated cisplatin at a dose of 20 mg/m(2)/day on D1-D5. The regimen was repeated every 3 weeks, totally for 6 cycles. RESULTS: Of the 141 evaluable patients, there were 104 men and 37 women, with a median age of 54 years (range, 23 - 80 years). Metastases before chemotherapy were detected in lymph nodes (46.8%), liver (40.4%), lung (5.7%) and other area (10.6%). The median treatment duration was 6 cycles (range, 3 - 6 cycles). The objective response rate (RR) was 36.2% (51/141). The median follow-up period was 17.5 months. The median time to progress (TTP) was 9.0 months, and the median overall survival (OS) was 12.0 months. The most common treatment-related adverse events (grade 3/4) were: hand-foot syndrome (HFS) (2.1%), leucopenia (0.7%), abnormal alanine transaminase elevation (2.8%). There was no treatment-related death. CONCLUSION: Capecitabine combined with fractionated cisplatin is highly effective and well tolerated as a first-line treatment for advanced gastric cancer, with comparable results to 5-Fu plus cisplatin combination therapy.

[Prospective non-randomized study of chemotherapy combined with radiotherapy versus chemotherapy alone in patients with metastatic or relapsed esophageal squamous cell carcinoma].

OBJECTIVE: To investigate the time to progression (TTP) and overall survival in patients with previously untreated metastatic or relapsed esophageal squamous cell carcinoma treated with chemotherapy (paclitaxel plus cisplatin) combined with radiotherapy versus chemotherapy alone, and also to evaluate the efficacy and toxicity of the regimen. METHODS: In this prospective and non-randomized study, 47 patients with definite measurable lesion and having no previous chemotherapy were enrolled. All patients were treated with paclitaxel 175 mg/m2 by 2-hour iv infusion on d1 and cisplatin 75 mg/m2 by iv infusion on d1, which were repeated every 21 days. After 2-6 cycles of chemotherapy, those who gained CR, PR or SD were non-randomly assinged into radiotherapy group (group A) or non-radiotherapy group (group B). RESULTS: Totally, 47 patients were enrolled into this study, and all of them were valuable for response. One patient achieved complete response (CR), 19 partial response (PR), 24 stable disease (SD), and 3 were found to have disease progression (PD). The overall response rate of chemotherapy was 42.6% (95% CI, 0.28-0.58). Twenty-one of these 47 patients were sequentially treated with radiotherapy. The median survival and TTP was 13 months and 10 months in the group A , versus 11 months and 5 months in the group B (P < 0.024, P < 0.015), respectively. The most common toxicities were neutropenia and alopecia. There were no grade 4 clinical toxicity and treatment-related death in this series. Systemic adverse effects frequently occurred during radiotherapy were esophagitis and fatigue, which were tolerable. CONCLUSION: The combined therapy using chemotherapy (paclitaxel + cisplatin) followed by radiotherapy is effective, tolerable, and statistically superior to chemotherapy alone in patients with metastatic or relapsed esophageal squamous cell carcinoma.

Etiology and prevention of gastric cancer: a population study in a high risk area of China.

A series of studies has been carried out in Linqu County, Shandong Province, China, a high-risk area for gastric cancer, to investigate the risk factors associated with gastric cancer, precancerous lesions and the prevention of gastric cancer. Our studies showed that sour pancakes (a popular local food), salted foods, cigarette smoking, and family history of gastric cancer were risk factors, whereas fresh vegetables, and intake of vitamin C and calcium were inversely associated with the risk of gastric cancer. The prevalence of chronic atrophic gastritis was approximately 20% in an adult population in Linqu County, intestinal metaplasia was approximately 50%, and dysplasia was approximately 20%. A follow-up study showed that the relative risk of developing gastric cancer increased with the severity of gastric lesions, and was associated with dietary factors, cigarette smoking and H. pylori infection in this population. The findings strongly support the idea that gastric cancer is primarily determined by environmental factors and develops in a multistep progression of precancerous lesions.

[Imatinib mesylate alone for refractory advanced gastrointestinal stromal tumor].

OBJECTIVE: To evaluate the efficacy and safety of imatinib mesylate in the treatment of patients as preoperative supplement, or used alone for unresectable and(or) metastatic gastrointestinal stromal tumor (GIST). METHODS: A total of 30 cases with advanced GIST were proved pathologically. Among them, CD117 was detected positive in 29 patients; 2 patients received imatinib mesylate before operation and 28 patients with unresectable and(or) metastatic GIST received oral imatinib mesylate daily at dose of 200-600 mg. Three patients were lost in follow-up and the objective effect was evaluated in 25 patients. RESULTS: Fifteen of 25 patients (60.0%) achieved partial response (PR); 5 (20.0%) had stable disease (SD) and 5 (20.0%) had progression disease (PD). Median time to progression (mTTP) was more than 13 months during which most experienced benefit. Twenty-two patients had been followed-up more then 1 year. The 1-year survival rate was 86.4%. The overall median survival has not been obtained to date. Twenty-seven patients were valuable for the toxicity assessment according to the WHO standard. The main toxicity included grade I-II edema of periorbital area and lower limb in 85.2% (23/27) patients, leukopenia was present in 40.7% (11/27) and intratumoral bleeding in 7.4% (2/27). Other toxicities included mild fatigue (29.6%), abdominal pain (14.8%), efflorescence (11.1%), nausea and vomiting (18.5%). CONCLUSION: As an inhibitor of tyrosine kinase, imatinib mesylate is generally well tolerated and has been proved to be effective and safe during prolonged treatment of patients with advanced gastrointestinal stromal tumors.

[The evaluation of LFH or LFPH in the treatment of advanced cancer of gastric cardia and colorectal cancer].

OBJECTIVE: To evaluate the therapeutic effects of hydroxycamptothecin (H) combined with leucovorin (L), fluorouracil (F) and cisplatin (P) on advanced cancer of gastric cardia and colorectal cancer. METHODS: Sixty-five patients with advanced cancer of gastric cardia or colorectal cancer were treated by LFH or LFPH regimen. All patients completed four cycles of treatment, in 21 days per cycle. RESULTS: The overall response rate (RR) was 26.2% (17/65) with partial response (PR) in 17 patients, stable disease (SD) in 31 and progressive disease (PD) in 17. The clinical benefit response rate (CR + PR + SD) was 73.8% (48/65). The RR were 32.3% (10/31) for untreated patients and 20.6% (7/34) for retreated patients. The stable rate was 47.7% (31/65). The RR of patients with cancer of gastric cardia were 33.3% (5/15) for untreated treatment and 29.4% (5/17) for retreated ones. Median survival time (MST) was 10 months. Median time to progression (MTTP) was 8 months. Grade 3 - 4 toxicities were stomatitis (10.8%), nausea and vomiting (12.3%) and leukopenia (6.2%). Most patients (> 80%) developed Grade 1 - 2 alopecia. CONCLUSION: The regimen of HCPT combined with LV, 5-Fu and DDP appears to be an effective and tolerable therapeutic option for advanced cancer of gastric cardia and colorectal cancer, especially for the former and retreated patients, giving a satisfactory stable rate though not very high.

[Three-dimensional spiral CT in advanced gastric cancer].

OBJECTIVE: To study the usefulness of three-dimensional spiral CT (3DCT) in the diagnosis of advanced gastric cancer (AGC). METHODS: Between June 1999 and December 2000, 54 patients with AGC were consecutively examined. On the 3D Virtuoso workstation, source images were uploaded to create a 3DCT volume block that was then processed with volume rendering technology (VA30C) to achieve virtual-reality endoscopy (VE), clipped volume block (CVB), and ray sum (RS). After the above scanning, all the patients were examined by a two-phase enhanced spiral CT (2DCT). The visualization, manifestation, and Borrman's classification of lesions in VE, CVB, RS, and 2DCT were evaluated and correlated with gastroscopic, surgical, and pathological findings. Respiratory artifact and gastric residue were also observed. RESULTS: (1) CVB showed the excellent visualization in 88.9% of cases, in contrast to VE and RS (50.0% and 38.9%) (P < 0.01). (2) The accuracy in evaluating mucous membrane, ulceration, lumen, wall, cardia, pylorus, and extension of the tumor were more than 90.0% except mucosa by RS (84.4%) and ulceration by VE (87.5%) or RS (81.6%) which was significantly different from CVB (96.0%) and 2DCT (96.1%) (P < 0.05). VE demonstrated an accuracy of 95.8% in diagnosis of mucosal abnormality. (3) The correct Borrman's classification was obtained in 83.3% cases by VE, 79.6% by CVB, 72.2% by RS, 88.9% by 2DCT and 85.2% by 3DCT with significant difference between 2DCT and RS (P < 0.05), but not between 3DCT and 2DCT (P > 0.05). (4) In addition to 2DCT which had no step-like artifacts, they were invisible in 53.7% of VE, 40.7% of CVB, and 81.5% of RS, with RS showing the least artifacts among 3DCT (P < 0.01). A few of gastric residues caused by pre-scanning intake of water to swallow effervescent agent could be found on 3DCT images which caused no evident influence on diagnosis. CONCLUSION: Additional information on the diagnosis of AGC can be obtained by use of 3DCT, especially the visualization of a lesion in clipped volume block and the observation of mucosa in virtual-reality endoscopy.

[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.

[Effects of fractionated low dose Cisplatin on renal functions of patients with gastric carcinoma].

BACKGROUND & OBJECTIVE: Cisplatin (DDP) in large dosage impairs renal functions, while the impact of fractionated low dose DDP on renal functions is unclear. This study was to evaluate the effects of fractionated low dose DDP on renal functions of gastric cancer patients. METHODS: From Sep. 1998 to Jun. 2002, 31 gastric cancer patients were treated with LFEP regimen at School of Oncology of Peking University: intravenous administration of calcium folinate (CF, 150 mg/m(2)) at Day 1-3, 5-fluorouracil (5-FU, 500 mg/m(2)) at Day 1-5, epirubicin (EPI, 60 mg/m(2)) at Day 1, and DDP (20 mg/m(2)) at Day 1-3. Urine N-acetyl-beta-D-glucosaminidase (NAG), gamma-glutamyl transferase (gamma-GT) and routine urine test were assessed before chemotherapy and every other day during the 14-day chemotherapy; serum creatinine (sCr) and urea nitrogen (BUN) were assessed at the 7th day and 14th day during treatment. RESULTS: Of the 31 patients, 13 had normal renal functions before chemotherapy, while only 1 had normal renal functions after chemotherapy. Urine NAG and gamma-GT were changed significantly after chemotherapy: they were increased significantly on the 4th day and maintained higher than normal level for another 14 days thereafter. Meanwhile, no significant change in sCr and BUN were observed. CONCLUSION: Combined chemotherapy with fractionated low dose DDP still adversely affects renal functions of gastric cancer patients, however, the long-term effects need to be clarified.

[Efficacy of gemcitabine-based chemotherapy on advanced pancreatic cancer].

BACKGROUND & OBJECTIVE: Advanced pancreatic cancer has a poor prognosis. Gemcitabine (GEM) can improve the quality of life of pancreatic cancer patients. However, the efficacy of gemcitabine-based combination chemotherapy is uncertain. This study was to compare the efficacy of GEM-based combination therapy and GEM alone on advanced pancreatic cancer. METHODS: Clinical data of 40 patients with pathologically or clinically diagnosed advanced pancreatic cancer were analyzed. Of the 40 patients, 15 were treated with GEM (1,000 mg/m(2)) alone weekly for 7 weeks followed by a 2-week rest, then received cycles of 3-week administration with 1-week rest; 25 were treated with GEM (1,000 mg/m(2)) weekly for 2 weeks plus 5-fluorouracil (5-FU) (425-600 mg/m(2)) as bolus at Day 1-5 or 120-hour infusion every 21 days, or cisplatin (DDP) (30-37.5 mg/m(2)) at Day 1-2 every 21 days, or oxaliplatin (85-130 mg/m(2)) at Day 1 every 21 days, or capecitabine (1,000 mg/m(2)) twice a day at Day 1-14 every 21 days, respectively. The survival was analyzed by Kaplan-Meier method. Median time to progression (mTTP), clinical benefit response (CBR), disease control rate, median overall survival (mOS) and toxicity were assessed according to World Health Organization criteria. RESULTS: The rate of CBR was 56.0% in GEM-combination group and 46.7% in GEM alone group. There were no significant differences in disease control rate, mOS, CBR, and adverse events between the two groups (all P>0.05). However, for the patients with stage III-IV advanced pancreatic cancer, the disease control rate was higher in GEM-combination group than in GEM alone group (75.0% vs. 45.5%, P=0.13). CONCLUSION: GEM-combination regimens and GEM alone have similar efficacy, and lead to similar clinical benefit response and mOS for the patients with advanced pancreatic cancer.

Randomized double-blind factorial trial of three treatments to reduce the prevalence of precancerous gastric lesions.

BACKGROUND: Randomized trials have yielded mixed results on the effects of treatment for Helicobacter pylori and little information on the effects of vitamins or garlic supplements on precancerous gastric lesions. We conducted a randomized trial to test the effects of one-time H. pylori treatment and long-term vitamin or garlic supplements in reducing the prevalence of advanced precancerous gastric lesions. METHODS: Most of the adults aged 35-64 years in 13 randomly selected villages in Linqu County, Shandong Province, China, were identified and given baseline endoscopies in 1994. In 1995, 3365 eligible subjects were randomly assigned in a factorial design to three interventions or placebos: amoxicillin and omeprazole for 2 weeks in 1995 (H. pylori treatment); vitamin C, vitamin E, and selenium for 7.3 years (vitamin supplement); and aged garlic extract and steam-distilled garlic oil for 7.3 years (garlic supplement). Subjects underwent endoscopies with biopsies in 1999 and 2003, and the prevalence of precancerous gastric lesions was determined by histopathologic examination of seven standard biopsy sites. The 3365 eligible randomized subjects represented 93.5% of those with baseline endoscopy and included all baseline histologic categories except gastric cancer. Only 0.18% had normal gastric mucosa. Logistic regression was used to estimate the intervention effects on the odds of advanced precancerous gastric lesions, and t-tests were used to assess effects on histologic severity. All statistical tests were two-sided. RESULTS: H. pylori treatment resulted in statistically significant decreases in the combined prevalence of severe chronic atrophic gastritis, intestinal metaplasia, dysplasia, or gastric cancer in 1999 (odds ratio [OR] = 0.77; 95% confidence interval [CI] = 0.62 to 0.95) and in 2003 (OR = 0.60; 95% CI = 0.47 to 0.75), and had favorable effects on the average histopathologic severity and on progression and regression of precancerous gastric lesions in 2003. H. pylori treatment did not reduce the combined prevalence of dysplasia or gastric cancer. However, fewer subjects receiving H. pylori treatment (19/1130; 1.7%) than receiving placebo (27/1128; 2.4%) developed gastric cancer (adjusted P = .14). No statistically significant favorable effects were seen for garlic or vitamin supplements. CONCLUSION: H. pylori treatment reduces the prevalence of precancerous gastric lesions and may reduce gastric cancer incidence, but further data are needed to prove the latter point. Long-term vitamin or garlic supplementation had no beneficial effects on the prevalence of precancerous gastric lesions or on gastric cancer incidence.