Study protocol of a randomized phase III trial of comparing preoperative chemoradiation with preoperative chemotherapy in patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma: PREACT.

BACKGROUND: The prognosis of patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma is still dismal. There are no standard treatment strategies for these patients. Multidisciplinary team (MDT) approach is a good choice for making a high-quality decision. Generally, MDT will recommend these patients to receive preoperative chemotherapy or preoperative chemoradiation based on all kinds of treatment guidelines. However, the preferred preoperative treatment is still not established. In order to solve this problem, we carry out this randomized phase III trial of comparing preoperative chemoradiation with preoperative chemotherapy in patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma. METHODS: Eligible patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma are randomized to receive preoperative chemoradiation or preoperative chemotherapy, followed by surgery and postoperative chemotherapy. In the preoperative chemoradiation arm (Pre-CRT), patients receive two cycles of S-1 and oxaliplatin (SOX), chemoradiation, then followed by surgery and three more cycles of SOX chemotherapy. In the preoperative chemotherapy arm (Pre-CT), patients receive three cycles of SOX, following surgery three more cycles of SOX are given. The primary endpoint of this trial is to verify that preoperative chemoradiation could significantly improve the 3-year disease free survival (DFS) of patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma compared to preoperative chemotherapy. DISCUSSION: The results from this trial will provide important information about whether preoperative chemoradiation could improve survival compared to preoperative chemotherapy among patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03013010. First posted January 6, 2017.

Influence of SLCO1B1 in gastric cancer patients treated with EOF chemotherapy.

Cytochrome-P450 enzymes, ATP-binding cassette transporters, and solute carriers mediate drug metabolism as metabolic enzymes and membrane transporters, respectively. The present study investigated whether single nucleotide polymorphisms (SNPs) in genes encoding these proteins were predictive or prognostic factors in patients with metastatic gastric cancer (MGC) undergoing chemotherapy. A retrospective study of 108 MGC patients who received epirubicin, oxaliplatin, and 5-fluorouracil (EOF) as first-line treatment was performed. A total of 13 SNPs were genotyped, including SLCO1B1 (rs4149056), SLC2A9 (rs16890979, rs6449213, rs734553), ABCG2 (rs2231142), CYP2C9 (rs1057910, rs1799853), CYP2C19 (rs72552267, rs28399504, rs56337013, rs41291556) and CYP1A2 (rs12720461, rs56107638). The associations between these genotypes and disease-control rate (DCR), progression-free survival (PFS) and overall survival (OS) were analyzed. Patients with SLCO1B1 rs4149056 TT genotype had a significantly shorter OS compared with those with a C allele (CC + CT; 312 vs. 565 days, P=0.039). Multivariate analysis revealed that the rs4149056 TT homozygous genotype was an independent prognostic factor for shorter OS (hazard ratio: 2.565, 95% confidence interval: 1.215-5.415, P=0.014). However, no significant associations between SLCO1B1 rs4149056 and PFS were observed, between the other 12 SNPs and PFS or OS, or between any of the 13 SNPs and DCR. In conclusion, SLCO1B1 rs4149056 TT may be an independent predictor of survival in patients with MCG treated with EOF chemotherapy.

Influence of hypoxia-related genetic polymorphisms on the prognosis of patients with metastatic gastric cancer treated with EOF.

Tumor hypoxia is common in a number of solid tumor types including gastric cancer, and is associated with treatment resistance and poor prognosis. The present study aimed to investigate the function of hypoxia-associated genetic polymorphisms in predicting treatment response and survival in patients with metastatic gastric cancer (MGC) treated with EOF (oxaliplatin and 5-fluorouracil combined with epirubicin) as first-line chemotherapy. The present retrospective study enrolled 108 Chinese patients with MGC receiving EOF as first-line chemotherapy, and genotyped six single nucleotide polymorphisms (SNPs) in four hypoxia-associated genes [myoglobin (MB) rs7292 and rs7293, ATP Binding Cassette Subfamily G Member 2 rs2231142, MutL homolog 1 (MLH1) rs1800734 and rs9852810, and Poly(ADP-Ribose) Polymerase 1 rs1136410]. The results of the present study indicated that the CT/TT genotype of MB rs7292, as well as the GG genotype of MLH1 rs9852810, were independent favorable predictive factors of progression-free survival [PFS; MB rs7292: hazard ratio (HR)=0.135, 95% confidence interval (CI)=0.057-0.321, P<0.001; MLH1 rs9852810: HR=0.494, 95% CI=0.267-0.913, P=0.024). Using a prognostic index based on the favorable SNPs for PFS (MB rs7292 CT/TT genotype, and MLH1 rs9852810 GG genotype), patients were classified into a low-risk group (involving one or two of the two SNPs) and a high-risk group (involving neither of the two SNPs), with a PFS of 180.0 and 117.0 days, respectively (P=0.002). The results of the present study demonstrated that the CT/TT genotype of MB rs7292 and the GG genotype of MLH1 rs9852810 were independent favorable predictive factors of PFS in patients with MGC treated with EOF. Identification of those SNPs in blood samples may allow for the prediction of the short-term efficacy of first-line EOF treatment in patients with MGC.

Phase II trial of preoperative chemoradiation plus perioperative SOX chemotherapy in patients with locally advanced gastric cancer.

BACKGROUND AND PURPOSE: The ideal treatment strategy of patients with locally advanced gastric adenocarcinoma is unclear. The aim of this study is to evaluate the efficacy and feasibility of preoperative chemoradiation in these patients. PATIENTS AND METHODS: All patients underwent laparoscopic exploration or exploratory laparotomy before chemoradiation. Patients received one cycle of S-1 and oxalipatin followed by concurrent radiation and chemotherapy, then underwent another cycle of S-1 and oxalipatin. Surgery was performed 6-8 weeks after completing radiochemotherapy. The rate of curative gastrectomy and survival were investigated. This trial was registered with ClinicalTrial.gov, number NCT02024217. RESULTS: From April 2012 to August 2014, 40 patients were enrolled in the trial, and 36 patients were assessable. The most common hematologic toxic effects were leukopenia (80.6%), neutropenia (69.4%), and thrombocytopenia (50%); the most common nonhematologic toxic effects were anorexia (50%), nausea (22.3%), and vomiting (13.9%). There were no treatment related deaths. A total of 33 patients underwent second exploratory laparotomy after preoperative chemoradiation, and 24 (67%) patients received curative gastrectomy. The rates of pathological complete response (pCR) were 13.9%. The medial survival time (MST) was 30.3 months. CONCLUSION: Preoperative chemoradiation may be an effective treatment strategy among patients with locally advanced gastric adenocarcinoma.

A multi-center phase II study and biomarker analysis of combined cetuximab and modified FOLFIRI as second-line treatment in patients with metastatic gastric cancer.

BACKGROUND: To evaluate the efficacy of cetuximab combined with modified FOLFIRI (mFOLFIRI) as a second-line treatment in metastatic gastric cancer patients and to identify potential biomarkers of clinical outcomes. METHODS: All 61 patients received an initial intravenous (IV) dose of cetuximab (400 mg/m2) and weekly doses (250 mg/m2) thereafter, starting on day 1. On day 2 of each 14-day period, patients received IV irinotecan (180 mg/m2), leucovorin (200 mg/m2), and an IV bolus dose of 5-FU (400 mg/m2) followed by a continuous infusion of 5-FU (2400 mg/m2) for 46 h. The primary endpoint was time-to-progression (TTP). RESULTS: The response rate (RR) was 33.3% among 54 evaluable patients. In the intention-to-treat analysis, median TTP was 4.6 months (95% confidential interval [CI]: 3.6-5.6 months) and median overall survival (OS) was 8.6 months (95% CI: 7.3-9.9 months). In univariate analyses, plasma vascular endothelial growth factor (VEGF) levels were correlated with clinical outcome. In patients with low (≤12.6 pg/ml) and high (>12.6 pg/ml) baseline plasma VEGF levels, RR values were 55.0% and 5.3%, respectively (P = 0.001); median TTP values were 6.9 months and 2.8 months, respectively (P = 0.0005); and median OS values were 12 months and 5 months, respectively (P <0.0001). None of these patients exhibited KRAS, BRAF, or PIK3CA mutations. CONCLUSIONS: Combination therapy comprising cetuximab and mFOLFIRI was well tolerated and active as a second-line treatment for patients with metastatic gastric cancer. Patients with low baseline plasma VEGF levels were associated with better clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov. NCT00699881 . Registered 17 June 2008 (retrospectively registered).

Influences of ERCC1, ERCC2, XRCC1, GSTP1, GSTT1, and MTHFR polymorphisms on clinical outcomes in gastric cancer patients treated with EOF chemotherapy.

This study investigated the associations between genetic polymorphisms of six genes involved in DNA repair, detoxification pathways, and fluoropyrimidine metabolism and clinical outcomes in MGC patients receiving EOF treatment. This retrospective study included 108 Chinese MGC patients receiving EOF as first-line chemotherapy. Nine single nucleotide polymorphisms (SNPs) of six genes (ERCC1 rs2298881, ERCC2 rs13181 and rs1799793, XRCC1 rs25487 and rs25489, GSTP1 rs1695, GSTT1 rs2266637, and MTHFR rs1801133 and rs1801131) were genotyped, and the associations between each SNP and clinical outcome were analyzed. XRCC1 rs25487 A allele was significantly associated with progression disease (PD) to EOF (p = 0.002), and patients with AA genotype had significantly poorer progression-free survival (PFS) (p = 0.001) and overall survival (OS) (p = 0.041) compared with patients with the G allele (GG + GA). ERCC2 rs13181 G allele was significantly associated with PD (p = 0.026), and G carriers (GG + GT) tended to have poorer PFS (p = 0.092) than TT homozygotes. ERCC2 rs1799793 GA genotype was associated with unfavorable PFS (p = 0.034) and a tendency toward poorer OS (p = 0.090) compared with GG homozygotes. Patients were categorized as either good (0 risk factors) or poor risk (≥1 unfavorable SNPs) using a prognostic index based on XRCC1 rs25487 AA, ERCC2 rs13181 (GG + GT), and ERCC2 rs1799793 GA genotypes, with median OS and PFS of 534 days, 281 days (p = 0.009) and 206 days, and 123 days (p < 0.001), respectively. These results suggest that the prognostic index comprising XRCC1 rs25487, ERCC2 rs13181, and rs1799793 polymorphisms may be a useful predictor of clinical outcomes in MGC treated with EOF.

Neutropenia predicts better prognosis in patients with metastatic gastric cancer on a combined epirubicin, oxaliplatin and 5-fluorouracil regimen.

Chemotherapy-induced neutropenia (CIN) reportedly indicated better prognosis for some cancers. We retrospectively analyzed 150 evaluable metastatic gastric cancer (MGC) patients who had received first-line EOF5 (combination regimen of epirubicin, oxaliplatin and 5-day continuous infusion of 5-fluorouracil) treatment. We divided patients into three groups according to the worst grade of CIN: absent group (grade 0), moderate group (grade 1-2) and severe group (grade 3-4). Multivariate analyses of overall survival (OS) proved moderate and severe CIN were important prognostic factors whether regarding CIN as a time-varying covariate (TVC) or not. Compared with absent CIN, hazard ratio (HR) for moderate and severe CIN were 0.31 (95% confidential interval (CI): 0.17-0.55; P < 0.001) and 0.36 (95% CI: 0.20-0.64; P = 0.001) respectively with TVC; and were 0.31 (95% CI: 0.17-0.56; P < 0.001) and 0.34 (95% CI: 0.19-0.61; P < 0.001) respectively without TVC. In progression-free survival (PFS) analyses, moderate and severe CIN showed similar results. In the landmark group (n = 122 patients) analyses with TVC, moderate and severe CIN remained prognostic factors for PFS, while only moderate CIN was prognostic factor for OS. CIN predicted longer OS and PFS in MGC patients treated with first-line EOF5 chemotherapy.

Prostate cancer Lncap stem-like cells demonstrate resistance to the hydros-induced apoptosis during the formation of spheres.

UNLABELLED: Prostate cancer is the second most common cancer in Western countries. Although various treatment options have been available, most of the patients have frequently observed recurrence even in successful initial treatment. These symptoms indicated an incurable prostate cancer treatment-resistant state. We aimed to investigate the characteristics of prostate cancer stem-like cells (PCSCs) and their formation of the Lncap spheres. PCSCs were enriched from prostate cancer Lncap cells in serum-free medium. Lncap stem-like cells displayed resistance against the hydros-induced apoptosis during the formation of spheres. Flow cytometry analysis revealed that these cells of Lncap spheres are mostly composed of G0-G1 phase cells. Western blotting and immunohistochemistry staining showed high expressions of Wnt/ß-catenin and hypoxia-inducible factor 1-alpha (HIF-1α) in the Lncap sphere differentiate into cells, indicating the characteristic of Lncap spheres "stemness" during the development of apoptosis resistance. These findings provide insights into the mechanisms of PCSCs resistant against chemotherapy. CONCLUSION: The underlying mechanism of PCSCs against hydros-induced apoptosis was mostly attributed to their highly expressed Wnt/ß-catenin during the formation of spheres.

Effects of IGF2BP2, KCNQ1 and GCKR polymorphisms on clinical outcome in metastatic gastric cancer treated with EOF regimen.

AIM: The present study analyzed Type 2 diabetes mellitus (T2D)-related gene polymorphisms and their impacts on chemotherapeutic response and survival in patients with metastatic gastric cancer (MGC). PATIENTS & METHODS: This retrospective study enrolled 108 MGC patients treated with first-line EOF chemotherapy (epirubicin, oxaliplatin and 5-fluorouracil combination chemotherapy). Eleven single nucleotide polymorphisms of five T2D-related genes were determined. RESULTS: Among the 11 single nucleotide polymorphisms, three (IGF2BP2 rs4402960, IGF2BP2 rs6769511 and KCNQ1 rs163182) were significantly associated with disease control rate and two (GCKR rs780093 and rs780094) were significantly associated with progression-free and overall survival. CONCLUSION: Our results suggest IGF2BP2 and KCNQ1 polymorphisms might be independent predictors of chemotherapeutic response, while GCKR polymorphisms might be independent predictors of survival in MGC patients treated with first-line EOF chemotherapy. Original submitted 30 June 2014; revision submitted 15 April 2015.

Epirubicin combined with oxaliplatin and 5-day continuous infusion of 5-fluorouracil as a first-line treatment for metastatic gastric cancer: treatment outcomes and analysis of prognostic factors.

PURPOSE: In order to confirm the efficacy, tolerability, and baseline prognostic factors of an epirubicin (EPR)-containing triplet regimen, the EOF5 regimen, in patients with metastatic gastric cancer (MGC), we conducted the phase II trial and retrospective analysis. METHODS: MGC patients received the EOF5 regimen (EPR 50 mg/m(2) and oxaliplatin (OX) 130 mg/m(2) on day 1 followed by continuous infusion of 5-fluorouracil (5-FU) 375-425 mg/m(2)/days for 5 days every 3 weeks). Log-rank tests were used for univariate analysis of time to progression (TTP) and overall survival rate (OS), and stepwise Cox proportional hazards regression modeling was performed to generate a prognostic index. RESULTS: A total of 158 patients received the EOF5 regimen. Of the 150 evaluable patients, complete remission, partial remission, and stable disease were observed in 5 (3.3%), 70 (46.7%), and 58 patients (38.7%), respectively. The median TTP and OS were 6.0 (95% CI 5.4-6.6) and 12.6 months (95% CI 8.2-16.9), respectively. Grade 3-4 neutropenia (44.0%), thrombocytopenia (25.3%), and anemia (6.7%) were recorded. A prognostic index that included liver and lung metastasis, ascites/pleural effusion, and baseline serum CA19-9 was used to categorize the patients into three groups: good risk (0 risk factors), moderate risk (1 or 2 risk factors), and poor risk (3 or 4 risk factors). The median OS for these groups was 30.4, 12.4, and 5.6 months, respectively (P < 0.001). CONCLUSIONS: EOF5 is an effective regimen and a suitable alternative for the first-line treatment of MGC. According to the prognostic index used in our study, patients with no risk factors have a better OS when treated with EOF5 than those with one or more risk factors.

LRP5 polymorphism-A potential predictor of the clinical outcome in advanced gastric cancer patients treated with EOF regimen.

PURPOSE: Wnt pathways control key biological processes that potentially impact on tumor progression and patient survival. The present study analyzed the polymorphism of lipoprotein-related receptor 5 (LRP5) (gene with key functions in Wnt signaling) and its impact on the response to chemotherapy and survival of patients with advanced gastric cancer (AGC). METHODS: A total of 107 consecutive patients with AGC treated with first-line chemotherapy of EOF regimen were enrolled in the present retrospective study. The association between single nucleotide polymorphism (SNP) of rs3736228 in LRP5 and the clinical outcomes of the patients was studied. RESULTS: The CC genotype of rs3736228 was significantly correlated with a higher disease control rate when compared to the CT and TT genotypes (89.3% and 61.8%, respectively, P<0.001). A univariate survival analysis also showed that the progression free survival (PFS) and overall survival (OS) for the patients with the TC and TT genotypes of rs3736228 were worse than for the patients with the CC genotype (PFS: 3.3 and 6.7 months, respectively, HR =0.454, P<0.001; OS: 8.1 months and 18.8 months, respectively, HR =3.056, P<0.001). A multivariate Cox model incorporates rs3736228 and clinical features, also identified rs3736228 was significantly associated with the PFS and OS. CONCLUSIONS: Our results firstly highlight the importance of LRP5 gene of Wnt pathway in the treatment of AGC and identify polymorphism of rs3736228 as independent predictor of disease control rate, PFS and OS in AGC patients treated with first-line chemotherapy of EOF regimen in the Chinese Han population.

Intensive chemotherapy failure in Burkitt's lymphoma with cavernous sinus involvement.

Burkitt's lymphoma is an aggressive B-cell lymphoma with rapid proliferative index, which makes it disseminate easily to distal sites, especially to bone marrow and the central nerve system. We report here a 22-year-old woman with Burkitt's lymphoma involving multiple organs, including kidneys, breasts, left ovary, and bone marrow at the time of diagnosis. The patient responded well to intensive chemotherapy before the onset of retro-orbital pain, vomiting, and photophobia. The contrast-enhanced T1-weighted image in a second magnetic resonance image (MRI) showed a 2 x 1.9 cm mass in her left cavernous sinus that was not found in her initial MRI. Central nervous system (CNS)-directed high-dose chemotherapy and whole-brain radiation could not change the final failed treatment outcome caused by the cavernous sinus involvement disseminating to her entire CNS. Further study should provide well-designed therapeutic strategies to Burkitt's patients with cavernous sinus involvement.

[Clinical significance in detection of immunoglobulin heavy chain clonal rearrangement in bone marrow of patients with B cell lymphoma].

OBJECTIVE: To explore the feasibility of semi-nested PCR technique for detection of immunoglobulin heavy chain (IgH) clonal rearrangement in bone marrow of B-cell lymphoma patient and to further evaluate its clinicopathological value. METHODS: Gene clonal rearrangement of IgH was detected by semi-nested PCR using primers of FR2 & FR3A in 105 bone marrow samples of patients with B-cell lymphoma. The PCR detection results were compared with the cytomorphology of bone marrow aspiration biopsy. The correlation between PCR detection results and clinicopathological factors were evaluated. RESULTS: Among 105 cases of B-cell lymphoma, bone marrow involvement was detected by PCR technique in 48 cases (45.7%), while only 22 cases (21.0%) were detected by bone marrow cytological analysis. There was a significant difference between two methods (P < 0.05), and the concordance rate was 71.4%. The incidence of bone marrow involvement at the time of initial diagnosis detected by PCR technique was 30.8% for diffuse large B cell lymphoma (DLBCL), 25.0% for follicular lymphoma (FL), and 100.0% for small lymphocytic lymphoma (SLL), respectively. Bone marrow involvement detected by PCR detection correlated with Ann Arbor stage. Rate of clonal IgH gene rearrangement by PCR in early B-cell lymphoma was lower than that in advanced stage B-cell lymphoma patients (P = 0.02). There was no statistically significant difference in efficacy between patients with positive and negative results detected by PCR (P > 0.05). But difference in complete response (CR) rate (23.3% and 46.3%) had significant difference (P = 0.019). CONCLUSION: Semi-nested PCR analysis may be an effective method for detection of abnormalities in bone marrow in patients with B-cell lymphoma and is superior to cytomorphology. The positive rate in patients with advanced Ann Arbor stage is higher than that in patients with early Ann Arbor stage, and patients with PCR negative result have more chances to achieved CR after treatment.

Chloroxoquinoline in combination with epirubicin, cisplatin and 5-fluorouracil in metastatic gastric cancer.

BACKGROUND/AIMS: The aim of this study was to evaluate the efficacy and tolerability of combination chemotherapy with epirubicin, cisplatin, 5-fluorouracil (ECF regimen), and Chloroxoquinoline in patients with metastatic gastric cancer. METHODOLOGY: Twenty-two patients with histologically confirmed metastatic gastric adenocarcinoma were treated with a combination of epirubicin 50 mg/m2 (day 1), cisplatin 60 mg/m2 (day 1), 5-fluorouracil 500 mg/m2 (days 1 to 5), and Chloroxoquinoline 400 mg (days 1 to 21), with the cycle repeated every three weeks. RESULTS: Twenty patients were evaluable for response. One case of (5%) complete response, seven of (35%) partial response, nine (45%) of stable disease, and three (15%) of progressive disease were observed, giving an overall treatment response rate of 40%. Median survival time was 9.4 months, median progression-free survival was 6.1 months, and the 1-year survival rate was 25%. Both hematologic and non-hemotologic toxicities were well tolerated and no treatment-related deaths occurred. In patients who received Chloroxoquinoline maintenance monotherapy after six cycles of the combination regimen, progression-free survival was nine months. CONCLUSION: The combination regimen demonstrated comparable efficacy and acceptable safety profiles in patients with metastatic gastric cancer. Chloroxoquinoline maintenance monotherapy has a tendency to increase progression-free survival.

[Prognosis of primary non-Hodgkin's lymphoma of the breast].

OBJECTIVE: To analyze the clinical characteristics and prognosis of primary non-Hodgkin's lymphoma of the breast (PNHLB). METHODS: The characteristics, treatment methods and outcomes of 45 patients with PNHLB were retrospectively analyzed. Chemotherapy including CHOP and CHOP-like regimens was administered in 43 patients, and monoclonal antibody therapy in 6 patients. Furthermore, 19 patients underwent radiotherapy after chemotherapy. RESULTS: Of these 45 patients, 37 patients had diffuse large B cell lymphoma (DLBCL), patients with T cell or mucosa-associated lymphoid tissue (MALT) lymphoma were 4, respectively. Overall response rate of first-line chemotherapy was 90.7%. Median overall survival (OS) and progression-free survival (PFS) of all patients was 6.82 and 4.25 years, respectively. The results of Cox regression model analysis showed that international prognostic index score (IPI) (RR = 5.682, P = 0.002) and Ann Arbor stage (RR = 1.836, P = 0.040) were negative independent prognostic factors for OS. Central nervous system involvement (RR = 1.107, P = 0.005) was a negative independent prognostic factor for PFS. CONCLUSION: The patients with PNHLB have early occurrence in lifespan. Most pathologic type was DLBCL. IPI and Ann Arbor stage are two independent prognostic factors for survival.

Phase I dose-escalating study of S-1 in combination with oxaliplatin for patients with advanced and/or metastatic colorectal cancer.

The purpose of this study was to determine the optimal dose of oxaliplatin, when combined with a fixed dose of S-1 (40 mg/m twice daily on days 1-14) on a 3-week schedule, for patients with advanced and/or metastatic colorectal cancer. Patients were required to have a histologically proven advanced or metastatic colorectal cancer for which they had received no previous chemotherapy. Oxaliplatin was administered intravenously on day 1 every 3 weeks. Patients were divided into two groups to receive two doses of oxaliplatin - 100 mg/m or 130 mg/m. Ten patients were enrolled in the study between March 2006 and July 2006, and were followed up until 50% of the patients progressed. All patients were evaluated for chemotherapy-related toxicity. The maximum tolerated dose was not reached during the first course. One of six patients experienced grade 3 thrombocytopenia at dose level 2 of oxaliplatin. Nonhematological toxicity was mild and tolerable. During the full course of treatment, complete response was achieved in two of the nine evaluated patients and partial response was achieved in one patient. The remaining six patients achieved stable disease during first two courses of therapy, and four patients remained stable at the time of the last follow-up. The median time to progression-free survival was 8.3 months. When combined with a fixed dose of S-1 80 mg/m, oxaliplatin administered at a dose of 130 mg/m is tolerable and recommended for phase II study.

Phase II clinical trial of advanced and metastatic gastric cancer based on continuous infusion of 5-fluorouracil combined with epirubicin and oxaliplatin.

PURPOSE: To evaluate the efficacy and tolerability of systematic treatment of unresectable advanced or metastatic gastric cancer (A/MGC) based on EOF5 regimen (the combination of epirubicin, oxaliplatin and 5-day continuous infusion of 5-fluorouracil). PATIENTS AND METHODS: Twenty-six patients (18 males, 8 females; age range, 35-72 years) with histologically confirmed metastatic (n = 23) or unresectable advanced (n = 3) gastric adenocarcinoma with (n = 6) or without previous chemotherapy (n = 20) were consented to receive EOF5 (epirubicin 50 mg/m(2) and oxaliplatin 130 mg/m(2) on day 1, followed by continuous infusion of 5-fluorouracil 375-425 mg/m(2) day(-1) on day 1-5), and the treatment cycle was repeated every 3 weeks. Responses to treatment and toxicity were evaluated every 2 cycles. RESULTS: In the first-line treatment group of 20 patients, complete (CR) and partial (PR) remission were observed in two (10%) and six (30%) patients, respectively with an overall response rate of 40%). Eleven (55%) patients showed stable (SD) and one (5%) progressive disease (PD). One-year survival rate, time to progression (TTP) and median overall survival (OS) were 45%, 9.7 and 12.5 months, respectively. In the second-line treatment group of six patients, the numbers of CR, PR, SD and PD were 0, 1, 4 and 1, respectively. Symptomatic response rates were 88.2, 76.9, 89.5, and 88.9% for abdominal pain, distention, anorexia and weight loss. The mean Karnofsky performance status score was increased (P < 0.001) and maintained after two and four cycles treatment. The major adverse events were nausea/vomiting, oral mucositis, peripheral neuropathy, phlebitis, constipation and myelosuppression. CTC grade 3 or 4 hematologic toxicities included leucopenia (7.7%), neutropenia (15.4%), thrombocytopenia (19.2%), and anemia (3.8%). No treatment-related deaths were recorded. CONCLUSIONS: EOF5 regimen shows good efficacy and an acceptable safety profile in A/MGC patients, and would be a suitable alternative regimen for this indication.

[Prognostic predictors of nasal NK/T cell lymphoma detected by immunohistochemical staining].

OBJECTIVE: To investigate the prognostic predictors of nasal NK/T cell lymphoma. METHODS: The clinicopathologic feature data of 61 patients with nasal NK/T cell lymphoma proven by pathological examination from Jan. 1997 to Jan. 2005 were collected. Expression of survivin, CD44, nm23, p53, Ki-67, MDR-1 and CD95 was detected by immunohistochemical staining in 30 patients with available histologic specimens. The correlation between these factors and prognosis were analyzed. RESULTS: In univariate analysis, performance status, LDH level, clinical stage, initial treatment response, CD56, Ki-67 and CD95 were found to be the prognostic factors associated with time to progression (TTP) in nasal NK/T cell lymphoma, while the performance status, B symptoms, LDH level, initial treatment response, Ki-67 and CD95 were demonstrated as prognostic factors related to overall survival. In multivariate analysis, clinical stage, initial treatment response and performance status were independent prognostic factors for TTP, while the latter two factors were independent prognostic factors of overall survival. CONCLUSION: Clinical stage and initial treatment response, and performance status are found to be independent prognostic factors for TTP, whereas the latter two factors are demonstrated as independent prognostic factors of the overall survival. Overexpression of Ki-67 may be an unfavorable prognostic factor, but overexpression of CD95 may be a favorable one.

[Result of phase II clinical trial of herceptin in advanced Chinese breast cancer patients].

OBJECTIVE: To observe the clinical efficacy and adverse effects of herceptin for advanced Chinese breast cancer patients. METHODS: Thirty-one pathologically proved advanced breast cancer women were treated by herceptin. In the first week, a loading dose 4 mg/kg was administered by intravenous infusion and from the second week, a routine dose of 2 mg/kg was given every week for at least 3 months. RESULTS: There were 2 CR, 6 PR, 7 SD, and 16 PD among 31 patients after treatment by herceptin, the response rate being 25.8%. In factors influencing the prognosis, age and general condition were factors favoring the results, and pathological type, site of metastasis, grade of her-2 over expression and prior treatment were irrelevant to the results. The adverse effects were mild but different from those of the common anticancer drugs. CONCLUSION: Herceptin is effective and well tolerated by the Chinese breast cancer patients.

[Vinorelbine plus cisplatin in the treatment of advanced non-small cell lung cancer previously treated with taxane-based chemotherapy].

OBJECTIVE: To evaluate the efficacy and toxicity of vinorelbine plus cisplatin in the treatment of advanced non-small cell lung cancer (NSCLC) previously treated with taxane-based chemotherapy. METHODS: Thirty patients (0 - 1 score ECOG performance status) with stage IIIB/IV NSCLC previously treated with taxane-based chemotherapy were eligible for the study. Fifteen patients received the regimen of vinorelbine plus cisplatin (NP), the others received mitomycin, vindesine plus cisplatin (MVP). RESULTS: The overall response rates were 13.3% in NP and 0 in MVP (P > 0.05). Time to progression was longer for NP patients than that for MVP ones (6 v 3 months, P < 0.05), so was median survival (9 v 6 months, P < 0.05). The 1-year survival rate of 40.0% in the NP group was significantly higher than that of 0 in MVP (P < 0.05). Grade III-IV toxicity was observed at a similar rate in both groups (P > 0.05), though both well tolerated. CONCLUSION: Regimen of vinorelbine plus cisplatin is appropriate for good performance status patients with advanced non-small cell lung cancer previously treated with taxane-based chemotherapy. Time to progression, median survival and 1-year survival are satisfactory in patients treated with NP, which is complicated with acceptable toxicity.