Prognostic factors for survival of patients with advanced gastric cancer treated with cisplatin-based chemotherapy

Purpose The present study evaluated baseline patient- or tumor-related prognostic factors in patients with advanced gastric adenocarcinoma. Patients and methods A total of 304 consecutive patients with newly diagnosed metastatic or recurrent gastric cancer treated with one or more cycles of cisplatin-based chemotherapy at the Korea Cancer Center Hospital were enrolled in the current study. Results Among the original 304 patients, only 4 patients were alive at the time of this analysis. The median survival for all patients was 7.3 (95% CI, 6.3–8.2) months. Five independent prognostic factors were identified by a multivariate analysis: poor performance status (hazard ratio [HR], 1.46; 95% CI, 1.32–2.92), elevated total bilirubin (HR, 2.04; 95% CI, 1.73–2.35), presence of peritoneal metastasis (HR, 1.73; 95% CI, 1.57–1.90), presence of bone metastasis (HR, 3.11; 95% CI, 2.69–3.53), and more than 1 metastatic site (HR, 1.22; 95% CI, 1.06–1.38). A prognostic index was constructed that divided the patients into a good (n = 162), moderate (n = 82), or poor (n = 60) risk group. The 1-year survival rates for the good, moderate, and poor risk groups were 34.6, 20.7, and 1.7%, respectively, and the survival differences among the groups were highly significant (P < 0.0001). Conclusion Five prognostic factors were identified from patients receiving first-line cisplatin-based chemotherapy for advanced gastric cancer. A simple prognostic index was then developed that produced distinct survival rates among the different risk groups. Therefore, this prognostic model could help clinicians and patients in clinical decision-making and treatment tailoring based on the estimated prognosis.     

Postprogression survival for first-line chemotherapy of patients with advanced non-small-cell lung cancer

BackgroundGiven the growing number of drugs available for non-small-cell lung cancer (NSCLC), an effect of first-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies. We examined the relation between postprogression survival (PPS) and OS in phase III trials of first-line chemotherapy for advanced NSCLC.Patients and methodsA literature search identified 69 trials that were published during the past decade. We partitioned OS into progression-free survival (PFS) and PPS and evaluated the relation between OS and either PFS or PPS. We also examined whether any association might be affected by the year of completion of trial enrollment.ResultsThe average PPS was longer in recent trials than in older trials (6.5 versus 4.4 months, P < 0.0001). For all trials, PPS was strongly associated with OS (r = 0.82), whereas PFS was moderately associated with OS (r = 0.43). The correlation between OS and PPS in recent trials was stronger than that in older trials (r = 0.89 and 0.66).ConclusionsOur findings indicate that, especially for recent trials, PPS is highly associated with OS in first-line chemotherapy for advanced NSCLC, whereas PFS is only moderately associated with OS.     

The addition of chemoradiation to adjuvant chemotherapy is associated with improved survival in lymph node-positive gastric cancer

BackgroundIn the ARTIST trial, chemoradiation did not improve disease-free survival (DFS) in gastric cancer patients treated with curative-intent surgery and adjuvant chemotherapy. Subgroup analysis suggested chemoradiation improved DFS in patients with lymph node (LN) metastases, but the role of adjuvant chemoradiation remains uncertain. This study sought to determine the role of adjuvant chemoradiation using population-based methods.MethodsSurveillance, Epidemiology and End Results-Medicare linked data from 2004 to 2013 was used to identify patients aged 66 and older with LN-positive gastric adenocarcinoma. Multivariable logistic regression evaluated factors associated with receipt of chemoradiation. The Kaplan-Meier method and Cox proportional hazards modeling were used to evaluate overall survival (OS).ResultsA total of 2409 patients with LN-positive gastric adenocarcinoma who underwent upfront surgical resection were identified; 309 (13%) received adjuvant chemotherapy and 407 (17%) received adjuvant chemotherapy and chemoradiation. Among all patients, median OS was 15 months. Median OS was 20 months for patients who received chemotherapy alone and 27 months for patients who received chemotherapy and chemoradiation (p < 0.05). Recent diagnosis, older age, tumor stage T3 or T4, and Charleston Comorbidity Index were associated with an increased hazard ratio for death (p < 0.05). Receipt of chemoradiation was associated with a decreased hazard ratio for death (p < 0.05).ConclusionsIn patients with LN-positive gastric adenocarcinoma, the addition of chemoradiation to adjuvant chemotherapy after upfront surgical resection was associated with improved survival irrespective of the extent of lymphadenectomy. These data suggest chemoradiation should be considered in patients with LN-positive gastric adenocarcinoma.     

Anemia is the strongest prognostic factor for outcomes of 5-fluorouracil-based first-line chemotherapy in patients with advanced gastric cancer

Objective: To examine the prevalence of anemia and its impact of hemoglobin (Hgb) levels in predicting outcomes of 5-fluorouracil (FU)-based first-line chemotherapy for patients with advanced gastric cancer (AGC). Methods: We collected data retrospectively from 511 consecutive patients treated with FU-based first-line chemotherapy as a routine clinical practice for AGC and followed up in two centers from 1995 to 2003. FU was given in combination with cisplatin (61%), taxanes (12%), anthracyclines (24%) and/or folinic acid (50%). Results: Hgb values were <10 g/dl in 41%, and patients with baseline Hgb levels <10 g/dl had significantly lower response rates (9%) than patients with Hgb≥10 g/dl (53%; P<0.001). In addition, Hgb<10 g/dl served as a predictor for disease progression (RR, 1.77; 95% CI, 1.42–2.21) and death (RR, 1.85; 95% CI, 1.48–2.32) along with chemotherapy response and performance status. Conclusion: Low baseline Hgb level is a strong and independent prognostic factor for the outcomes of AGC patients receiving FU-based first-line chemotherapy. This results strongly suggest that Hgb level, along with performance status, may be considered as a stratification variable in subsequent studies of AGC.     

A randomized,phase II study of vandetanib maintenance for advanced or metastatic non-small-cell lung cancer following first-line platinum-doublet chemotherapy

Background

This randomized, phase II study investigated whether benefit could be obtained by giving vandetanib, an oral inhibitor of vascular endothelial and epithelial growth factor receptor, as a maintenance treatment in non-small cell lung cancer (NSCLC).

Methods

Patients were randomly assigned to either vandetanib or placebo after completion of 4 cycles of first-line chemotherapy. A progression-free survival (PFS) rate at 3 months was selected as the primary endpoint. We set a maximum PFS rate at 3 months to 30% (null hypothesis), and a minimum PFS rate at 3 months to 50% (alternative hypothesis).

Results

At the interim analysis, 9 of 24 patients in the vandetanib arm were progression-free at 3 months, whereas 7 of 24 in the placebo arm were progression-free. The placebo arm was closed at the first stage. The vandetanib arm proceeded to the second stage, and recruited a total of 75 patients. At the second stage, 28 out of 63 evaluable patients receiving vandetanib achieved PFS at 3 months. The alternative hypothesis that the PFS rate at 3 months is at least 50% was accepted. The median PFS was 2.7 months (95% CI, 1.9–4.4 months) in the vandetanib arm and 1.7 months (95% CI, 0.9–2.6 months) in the placebo arm. The most common adverse events in patients receiving vandetanib were rash (77.3%) and diarrhea (60.0%).

Conclusions

Maintenance therapy with vandetanib for patients with NSCLC after standard platinum doublet chemotherapy is well tolerated and may prolong PFS compared with placebo, and needs additional investigation.     

紫杉醇联合卡培他滨一线治疗晚期胃癌的临床观察

目的　观察紫杉醇联合卡培他滨一线治疗晚期胃癌的疗效和毒副反应。方法　晚期胃癌患者２０例,给予紫杉醇８０ｍｇ／ｍ２静脉滴注,第１、８天;卡培他滨１０００ｍｇ／ｍ２,分早晚各口服１次,第１～１４天;２１天为１周期。每２周期评价疗效。结果　１９例可评价疗效,获ＣＲ１例,ＰＲ７例,总有效率（ＲＲ）为４２.１％。中位无进展生存期和总生存期分别为４.８个月和９.７个月,１年生存率为３６.８％。主要的毒副反应为血液学毒性、脱发和手足综合症。结论　紫杉醇联合卡培他滨治疗晚期胃癌安全、有效,值得临床进一步应用。     

含紫杉醇方案一线治疗379例进展期胃癌的临床观察

目的 评价以紫杉醇为基础的联合化疗方案一线治疗进展期胃癌的疗效和安全性,为进展期胃癌的一线治疗策略制定提供依据。方法 回顾性分析本院2003年1月至2008年12月收治的379例进展期胃癌患者,根据化疗方案实施情况分为4组：紫杉醇+奥沙利铂+亚叶酸钙+氟尿嘧啶（A组,n=95）、紫杉醇+亚叶酸钙+氟尿嘧啶（B组,n=167）、紫杉醇+奥沙利铂（C组,n=94）和单药紫杉醇（D组,n=23）。分析4组的有效率（RR）、疾病控制率（DCR）、无进展生存期（PFS）和总生存期（OS）及治疗期间的毒副反应。结果 A、B、C和D组的RR分别为47.3％、52.1％、60.0％和39.1％,DCR分别为89.2％、92.6％、89.5％和69.6％,中位OS分别为11.4、11.7、11.7和7.5个月,中位PFS分别为6.6、7.2、7.2和4.1个月。3～4级不良反应中仅白细胞减少在4组中的发生率均超过25.0％,其余3～4级不良反应发生率低于20.0％;A组中3～4级恶心呕吐、疲乏及白细胞减少的发生率高于其余3组（P＜0.05）。结论 以紫杉醇为基础的联合化疗方案可作为进展期胃癌的一线治疗方案。     

Recent advances in chemotherapy for advanced gastric cancer

Although medical treatment has been shown to improve quality of life and prolong survival, no significant progress has been made in the treatment of advanced gastric cancer (AGC) within the last two decades. Thus, the choice of optimum standard first-line chemotherapy regimen for AGC remains debatable, and most responses to chemotherapy are partial and of short duration, with a median survival of approximately 7-11 mo and survival at 2 years rarely more than 10%. Recently, remarkable progress in tumor biology has led to the development of new agents that target critical aspects of oncogenic pathways. For AGC, several molecular targeting agents are now under evaluation in international randomized studies, and trastuzumab, an anti-HER2 monoclonal antibody, has shown antitumor activity against HER-2 positive AGC. However, this benefit is limited to only about 20% of patients with AGC (patients with HER-2 positive AGC). Therefore, there remains a critical need for both the development of more effective agents and the identification of predictive and prognostic molecular markers to select those patients who will benefit most from specific chemotherapeutic regimens and targeted therapies.     

胃动脉插管化疗栓塞联合腹腔化疗治疗进展期胃癌

目的:为探讨对晚期进展期胃癌,进行胃动脉化疗栓塞并腹腔化疗双途径给药的可行性及临床疗效.方法:无法手术切除的进展期胃癌98例,随机分为三组,A组行胃动脉化疗栓塞并腹腔化疗;B组行腹腔化疗;c组行静脉化疗.结果:胃动脉化疗栓塞是可行的.A、B、C三组有效率分别为71.88%、38.7%和14.3%.A组与B、C组比较有明显差异(P<0.01).A组有5例完全缓解,且生存期延长.不良反应以胃肠道毒性和骨髓抑制为主.A组术后胃粘膜有损伤,四周后可恢复正常.结论:胃动脉化疗栓塞并腹腔化疗双途径给药是治疗晚期进展期胃癌的有效方法.     

Long-term results for patients with unresectable gastric cancer who received chemotherapy in the Japan Clinical Oncology Group (JCOG) trials

Background. Despite recent developments in chemotherapeutic trials, the long-term results of chemotherapy remain to be clarified. We evaluated the impact of chemotherapy on long-term survival in patients with unresectable gastric cancer. Methods. Between 1985 and 1991, a total of 363 patients with gastric cancer were enrolled into a single randomized phase II study and into three series of phase II studies of the Japan Clinical Oncology Group. The chemotherapy regimens consisted of tegafur + mitomycin C (FTM), uracil-tegafur + mitomycin C (UFTM), 5′deoxy-flurorouridine + cisplatin (5′P), etoposide + doxorubicin + cisplatin (EAP), and 5-fluorouracil + cisplatin (FP). After a review of the 363 patients' case records, 226 patients who fulfilled the criteria of having "unresectable" factors prior to chemotherapy became the subjects for this analysis. Of the 226 patients, 50 were in the FTM regimen group, 39, in the UFTM; 49, in the 5′P; 42, in the EAP; and 46, in the FP group. Survival was updated continually. Results. Of the 226 patients, 22 (10%) survived longer than 2 years, and 8 (4%) have survived longer than 5 years. The 8 5-year survivors consisted of 6 patients who had para-aortic node metastases alone as an "unresectable factor", 1 who had para-aortic and cervical node metastases, and the remaining patient who had liver metastasis alone. Twenty-nine patients with para-aortic node metastasis alone had a significantly longer survival than the other 197 patients (P < 0.001). Conclusion. Systemic chemotherapy may offer some hope of achieving long-term survival in patients with unresectable gastric cancer, particularly when the patient has metastasis only to para-aortic nodes. Revieved: July 24, 2000 / Accepted: November 7, 2000     

Prospective randomized trial of short-term neoadjuvant chemotherapy for advanced gastric cancer

Background

We performed short-term neoadjuvant chemotherapy (s-NAC) to examine whether anticancer drugs can change the proliferative ability of cancer cells in gastric cancer patients.

Methods

Chemotherapy was performed for 72 h before gastrectomy in 63 gastric cancer patients. Patients were classed into four groups: Group F, 16 cases who received a single administration of 5-fluorouracil (5-FU); Group C, 15 cases who received a single administration of cis-diamminedichloroplatinum (CDDP; cisplatin); Group FC, 16 cases who received both 5-FU+CDDP; and a Control group, 16 cases who did not receive chemotherapy. We reviewed neoadjuvant biopsy tissue and gastric cancer tissue delivered by operation in these cases. The TUNEL method and immunohistochemistry with an anti-MIB-1 antibody were used to evaluate cellular apoptosis and proliferative ability, respectively. The apoptotic index (AI) and an MIB-1 index (MI) were also calculated.

Results

There were no differences in AI or MI in biopsy tissue between the groups. The AI of gastric cancer tissue in Group FC was significantly higher than in the other groups (P < 0.01). The MI of Group FC was significantly lower than in the other groups (P < 0.05). In addition, after s-NAC operation there was a significant inhibition of proliferative potency and an induction of apoptosis in Group FC.

Conclusion

Combination of CDDP and 5-FU reduced proliferative potency and increased cellular apoptosis in gastric cancer cells.     

Multicenter phase II study of weekly paclitaxel plus cisplatin combination chemotherapy in patients with advanced gastric cancer

Purpose Since a weekly administration of paclitaxel has demonstrated a sustained efficacy and more favorable toxicity profile than a 3-weekly administration for various solid tumors, the present study was conducted to evaluate the efficacy and safety of a combination regimen of weekly paclitaxel plus cisplatin in patients with advanced gastric cancer. Patients and methods Patients with previously untreated metastatic or recurrent, measurable gastric cancer received intravenous paclitaxel 100 mg/m² plus cisplatin 35 mg/m² on days 1 and 8 based on a 3-week cycle. Results Fifty-two patients were enrolled in the current study. Two complete responses and 17 partial responses were confirmed, giving an overall response rate of 36.5%. At a median follow-up of 8.5 months, the median time to progression and median overall survival was 6.0 and 10.8 months, respectively. Grade 3 neutropenia occurred in ten patients, while no grade 4 neutropenia or febrile neutropenia was observed. The most common non-hematologic toxicity was nausea (grade 1/2, 56.9%). There were no treatment-related deaths. Conclusion A weekly paclitaxel and cisplatin combination was found to be well-tolerated and effective in patients with advanced gastric cancer. Accordingly, this regimen can be regarded as an important first-line treatment option for advanced gastric cancer.     

ＸＥＬＯＸ方案治疗进展期胃癌的临床观察

目的　探讨奥沙利铂联合卡培他滨（ＸＥＬＯＸ）方案一线治疗进展期胃癌的疗效和不良反应。方法　回顾性分析７１例经病理组织学检查证实的胃癌患者,给予ＸＥＬＯＸ方案化疗,具体为：奥沙利铂１３０ｍｇ／ｍ^２静滴,第１天;卡培他滨１０００ｍｇ／ｍ^２口服,２次／日,第１～１４天,２１天为１周期。记录治疗的有效率（ＲＲ）、疾病进展时间（ＴＴＰ）、总生存时间（ＯＳ）和不良反应。结果　７１例患者共完成３２０个周期化疗,ＲＲ为４３７％（９５％ＣＩ：３６.３％ ～６２.９％）,包括ＣＲ５例（７.０％）,ＰＲ２６例（３６.６％）,中位ＴＴＰ为７.５个月（９５％ＣＩ：６.４～８.５个月）,中位ＯＳ为１１个月（９５％ＣＩ：８.２～１３.８个月）。主要不良反应以１～２级为主,３级不良反应包括恶心呕吐４例、腹泻５例、外周感觉神经症状５例、手足综合征７例和中性粒细胞缺乏６例,无化疗相关性死亡。结论　ＸＥＬＯＸ方案一线治疗进展期胃癌疗效较好,毒副反应可以耐受,使用方便,值得临床进一步研究。     

宫颈癌患者五年生存及影响因素分析

目的 观察宫颈癌患者生存与病情进展状态,并探究其影响因素,为改善预后提供依据.方法 本研究纳入2013年1月—2015年12月于哈尔滨医科大学附属肿瘤医院就诊的2306例宫颈癌患者,对其进行回顾和随访,采用Kaplan-Meier法分析宫颈癌患者总生存期(OS)和无进展生存期(PFS),用Cox风险比例回归模型分析生存...     

Evolving options for the treatment of metastatic breast cancer: progression-free survival as an endpoint

Because of its direct clinical relevance, overall survival is the gold standard endpoint for measuring clinical efficacy. However, achieving improvements in overall survival can be confounded by factors such as crossover to active treatment arms and subsequent treatment with non-experimental active therapies. Powering studies to detect significant overall survival increases requires prohibitively large patient numbers and long follow-up and may not always be practical. Trials incorporating progression free survival (PFS) or time to progression (TTP) as primary outcome measures are likely to be shorter, require fewer patients and are usually more affordable, which may ultimately translate into a more rapid evaluation of potentially effective experimental therapies. In heavily pretreated metastatic breast cancer, significant improvements in progression-free survival may indicate a clinically meaningful benefit for patients with otherwise limited salvage therapy options available. Approval for several newer agents in the advanced resistant or refractory metastatic breast cancer setting has been based on prolonged progression-free survival or time to progression as primary trial endpoints. In this paper, clinical trial data relating to OS, PFS and TTP endpoints are reviewed and the use of surrogate markers of survival for the evaluation of new drugs is considered.     

A phase II study of irinotecan and docetaxel combination chemotherapy for patients with previously treated metastatic or recurrent advanced gastric cancer

Purpose  Irinotecan (I) and docetaxel (D), each of which has a unique mechanism of action, were recently introduced in the treatment of patients with advanced gastric cancer (AGC). We have evaluated the efficacy and safety of the ID combination for AGC patients after failure of fluoropyrimidine- or platinum-based chemotherapy. Materials and methods  Patients with relapsed or progressive AGC after prior fluoropyrimidine- or platinum-based chemotherapy were treated with I (160 mg/m², 90 min) followed by D (65 mg/m², 1 h) every 3 weeks. Because of the unacceptable toxicity among the first ten patients, the doses were reduced for I (120 mg/m²) and D (50 mg/m²) every 3 weeks. Results  Forty-nine patients, of median age 53 years (range, 27–68 years), were treated with 170 cycles of chemotherapy (median, 2 cycles; range, 1–12 cycles). Three patients achieved complete response and seven achieved partial response, resulting in an overall response rate (ORR) of 20.4% [95% confidence interval (CI), 9.1–31.7%], with a median duration of 7.1 months (range: 2.1–69.1 months). ORR was 60% (95% CI, 29.6–90.3%) for the higher dose and 10.3% (95% CI, 0.7–19.8%) for the lower dose. Median time to progression for all patients was 2.7 months (95% CI, 1.7–3.8 months) and the median overall survival was 8.9 months (95% CI, 6.6–11.3 months). Grade 3/4 toxicities included neutropenia (90%), febrile neutropenia (50%), asthenia (40%), and diarrhea (10%) with the higher dose and neutropenia (71%), febrile neutropenia (11%), diarrhea (24%), and asthenia (24%) with the lower dose. There were two possible treatment-related deaths. Conclusion  The combination of irinotecan and docetaxel, once every three weeks shows anti-tumor activity but is not feasible as a second-line treatment for AGC patients after failure of fluoropyrimidine- or platinum-based chemotherapy due to the high rate of toxicities. S. J. Sym and H. M. Chang have contributed equally to this article.     

奥沙利铂联合卡培他滨一线治疗进展期胃癌的临床疗效观察

背景与目的：奥沙利铂联合卡培他滨（XELOX方案）是治疗进展期胃癌（advanced gastric cancer,AGC）的有效方案,但是该方案作为一线方案治疗AGC患者的疗效和安全性尚不确定。本研究旨在探讨XELOX方案作为一线方案治疗AGC的疗效及安全性。方法：33例既往未接受过化疗的AGC患者采用XELOX方案化疗．奥沙利铂130mg／m^2,静脉滴注2h,d1;卡培他滨2000mg／m^2,分2次口服．d1～14,21天为一个周期。患者最多接受8个周期化疗。结果：33例患者共接受159个周期的化疗,中位化疗周期数为5个。31例患者可评价疗效,其中完全缓解1例（3．2％）,部分缓解16例（51．6％）,稳定8例（25．8％）,进展6例（19．4％）。客观有效率54．8％（95％可信区间37．3％-72．3％）,临床获益率80．6％（95％可信区间66．7％～94．5％）。平均随访10．5个月,中位疾病进展时间5．9个月（95％可信区间4．7～7．1个月）,中位生存时间10．4个月（95％可信区间7．9～12．9个月）。常见不良反应有骨髓抑制、外周神经毒性、胃肠道反应、手足综合征等,经对症治疗后均好转．无治疗相关性死亡。结论：XELOX方案一线治疗AGC疗效显著,耐受性良好。     

A phase I combination chemotherapy study of biweekly paclitaxel and S-1 administration in patients with advanced gastric cancer

The aim of the current study was to determine the maximum tolerated dose (MTD) and the dose limiting toxicity (DLT) of a combination of paclitaxel and S-1 in patients with advanced gastric cancer. Fifteen patients were enrolled. The dose for S-1 was set at 80 mg/m²/day (days 1–14), while the dose for paclitaxel increased by 10 mg/m² for every three patients, with a starting dose of 100 mg/m² and was given biweekly on day 1 and 15. There was no severe toxicity (grade 4) recorded in patients receiving up to 120 mg/m² of paclitaxel. Leukopenia/neutrophilia with grade 1 to 3 occurred in six patients up to level 3. At 130 mg/m² of paclitaxel, grade 4 leukocytopenia and neutropenia events and grade 3 diarrhea developed in one out of three patients. One patient in another group of three patients that were enrolled at level 3, developed grade 4 granulocytopenia with fever (a body temperature higher than 38°C) and grade 3 leukocytopenia. Eight patients, out of a total of 15, showed a partial response, resulting in an objective response rate of 53%. Five patients received gastrectomy. Median survival time was 428 days and the 1 year survival rate was 53%. Biweekly paclitaxel/S-1 combination chemotherapy could be safely used for the treatment of advanced gastric cancer. The recommended doses for a phase II study with paclitaxel and S-1 are 120 mg/m² and 80 mg/m², respectively.