A novel treatment protocol with 6 cycles of neoadjuvant chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in stage III primary ovarian cancer

BackgroundFew prospective studies investigated neoadjuvant chemotherapy (NAC), interval cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in advanced ovarian cancer. We report the results of a phase II study where 6 rather than 3 cycles of NAC, followed by CRS and HIPEC, were adopted (HIPEC_ovaio, EudraCT number 2007-005674-31).Materials and methodsBetween 2007 and 2014, 56 patients with stage III primary ovarian cancer and peritoneal carcinomatosis were assigned to 6 cycles of platinum and taxane-based NAC. Of these, two had progression, 8 underwent palliative surgery, and 46 had CRS and HIPEC.ResultsA complete pathological response was observed in 9 patients. Of 46 patients who completed the treatment protocol, 29 had no macroscopic residual tumor. Postoperative grade III morbidity rate was 28.2%; no grade IV complications or mortality events were observed. Five-year overall survival (OS) of the entire series was 36 ± 7% (median: 36, 95% CI: 26–45 months). In 46 patients treated by CRS and HIPEC, 5-year OS was 42 ± 8% (median: 53, 95% CI: 29–76 months), and 5-year progression-free survival was 26 ± 7% (median: 23, 95% CI: 19–27 months). Completeness of cytoreduction, peritoneal cancer index and FIGO stage resulted as significant prognostic factors.ConclusionsA novel protocol consisting of 6 cycles of NAC, followed by CRS and HIPEC, is associated with notable improvement in peritoneal carcinomatosis, limited postoperative morbidity risk and high survival rates in responders, and could deserve further investigations in randomized clinical trials.     

Phase 2 study of intraperitoneal topotecan as consolidation chemotherapy in ovarian and primary peritoneal carcinoma

BACKGROUND: Intravenous topotecan is approved for the treatment of ovarian cancer (OC). In intraperitoneal (i.p.) topotecan studies, 20 mg/m(2) dosing was tolerable. This study evaluated the feasibility, safety, and preliminary efficacy of i.p. topotecan as consolidation chemotherapy in patients with OC or primary peritoneal cancers (PPCs). METHODS: Patients with stage III/IV ovarian or PPC in clinical complete response after surgical cytoreduction and intravenous carboplatin/paclitaxel chemotherapy who had benign findings or minimal persistent disease (< or = 1 cm diameter) at second-look surgery were eligible. Intraperitoneal topotecan 20 mg/m(2) was infused once every 21 days for 4 to 6 cycles. Kaplan-Meier estimates were used to calculate progression-free survival (PFS) and overall survival (OS). RESULTS: Twenty patients were enrolled (18 [90%] patients had OC). Sixteen patients received 4 cycles, 3 patients received 6 cycles, and 1 patient withdrew after 1 cycle. The mean delivered dose was 18 mg/m(2). Grade 3/4 toxicities included neutropenia and thrombocytopenia (45% for both). Grade 1/2 abdominal distension and nausea were reported in 60% and 40% of patients, respectively. Median PFS was 24 months from second-look surgery (95% confidence intervals [CI]: +/-10 months). Sixteen patients were alive and median OS was not reached at the time of data analysis. OS estimated at either 30 months from second-look surgery, or 3 years from initial diagnosis, was 84% (95% CI, 68%-100%). CONCLUSIONS: Consolidation i.p. topotecan is a feasible option for women withadvanced ovarian and primary peritoneal cancers. Further investigation of i.p. topotecan is warranted in this patient population.     

Randomized controlled trial of neoadjuvant chemotherapy with cisplatin and vinorelbine in patients with stage IIIA non-small cell lung cancer in China

Aim:   The aim of this study was to evaluate the efficacy of cisplatin plus vinorelbine as a regimen of neoadjuvant chemotherapy on the improvement of surgical resectability and survival in Chinese patients with stage IIIA non-small cell lung cancer (NSCLC).
Methods:   Fifty-six patients with stage IIIA NSCLC were randomly assigned to undergo either surgery preceded by two cycles of chemotherapy with cisplatin plus vinorelbine (the neoadjuvant chemotherapy arm) or immediate surgery (the primary surgery arm). The patients who had a complete resection received two to four cycles of chemotherapy, and those with incomplete resection received radiotherapy followed by two cycles of chemotherapy after surgery.
Results:   The overall response rate to neoadjuvant chemotherapy was 53.6%, with a complete response of 7.1%. A pathological complete response was seen in two patients (8%). The complete resection rates were 78.6% in the neoadjuvant chemotherapy arm and 60.7% in the primary surgery arm. The median overall survival and median disease-free survival was 30 months and 24 months, respectively, in the neoadjuvant chemotherapy arm as compared to 16 months and 11 months in the primary surgery arm ( P  = 0.04 and P  = 0.048). The 3-year and 5-year survival rate was 49.7% and 31.9%, respectively, for the neoadjuvant chemotherapy arm and 29.2% and 3.6% for the primary surgery arm.
Conclusion:   Neoadjuvant chemotherapy with cisplatin plus vinorelbine regimen is effective and tolerable and can improve the overall survival and disease-free survival time in Chinese patients with stage IIIA NSCLC.     

Neoadjuvant chemotherapy in advanced gastric cancer with non-curative factors: a Phase II study with 5-fluorouracil, leucovorin, and cisplatin

Background. Neoadjuvant chemotherapy (NAC) has recently received increasing attention in an attempt to increase the rate of complete tumor resections, reduce systemic metastases, and prolong survival in patients with advanced gastric cancer. Methods. Since 1993, 21 patients with unresectable or non-curative resectable gastric cancer received NAC, consisting of 5-fluorouracil, leucovorin, and cisplatin (FLP) with at least two cycles before surgery. Results. All except 2 patients underwent surgical treatment, and resection was performed in 18 (85.7%). There were no deaths and no major morbidity following operation. There was no complete response (CR), but 12 patients (57.1%) had a partial response (PR), the response rate was 47.6% for the primary region, 64.7% for abdominal para-aortic (No.16) lymph node metastasis, 40.0% for liver metastasis, and 11.1% for peritoneal dissemination. One-year survival of the 21 patients was 40.5%, and median survival time (MST) was 322 days. MST in the responders was 571 days, and that in non-responders was 199 days (P < 0.01). MST was 835 days in patients who underwent curative resection and 310 days in those who underwent non-curative surgery (P < 0.01). There was no grade 4 toxicity, but grade 3 leukopenia occurred in 4 patients (19.0%), grade 3 anemia occurred in 3 patients (14.3%), and grade 3 stomatitis in 2 patients (9.5%). There were no serious renal disorders and no treatment-related death. Conclusions. The combination of FLP for NAC was feasible and useful for tumor reduction, especially for No.16 lymph node metastasis. There was a survival benefit in patients whose tumor had PR or who had had curative resection. We should confirm the effect and survival benefit of FLP for NAC by a prospectively randomized clinical controlled study. Received for publication on Jan. 19, 1999; accepted on March 15, 1999     

奥沙利铂联合卡培他滨一线治疗进展期胃癌疗效观察简

目的：观察奥沙利铂（L—OHP）联合卡培他滨治疗进展期胃癌的近期疗效和毒副反应。方法：经病理学或细胞学确诊的42例晚期患者,应用L—OHP130mg／m^2,静滴2h,d1,每3周为1周期,卡培他滨2000mg／（m^2·d）,分2次口服,第1—14天,42例患者至少接受2个周期化疗后评价疗效及不良反应。结果：42例均可评价疗效,CR2例（4．76％）,PR20例（47．62％）,SD14例（33．33％）,PD6例（14．29％）,总有效率为52．38％（22／42）,中位疾病进展时间（TTP）为6．1个月,中位生存期10．0个月。毒副反应主要为手足综合征、恶心呕吐、骨髓抑制等,多为Ⅰ—Ⅱ级毒性反应,可耐受,无化疗相关死亡者。结论：XELOX方案在晚期胃癌的治疗中疗效较为肯定,不良反应可耐受。     

同步放化疗对不能手术局部晚期胃癌的疗效

目的:观察同步放化疗对不能手术的局部胃癌晚期（Ⅱ-Ⅲc）患者的近期疗效。方法:将55例不能手术的局部晚期胃癌患者随机分为2组,28例进行同步放化疗治疗,先行XELOX方案化疗1周期,于2周期化疗第2天同时进行适形放疗,并按化疗周期进行3、4周期XELOX方案治疗。27例患者进行4周期XELOX方案化疗。结果:无进展生存期（PFS）:同步放化疗组为7.11个月,化疗组为5.13个月 (P＜0.05);一年生存率同步放化疗组60%高于化疗组51%,两者比较,无统计学意义(P＞0.05);肿瘤客观缓解率（ORR）同步放化疗组67.8%,化疗组40.7%（P＜0.05）;患者卡氏评分两组治疗前后均无统计学意义(P＞0.05)。结论:同步放化疗可以提高不能手术局部晚期胃癌患者近期疗效。     

Chronicle: results of a randomised phase III trial in locally advanced rectal cancer after neoadjuvant chemoradiation randomising postoperative adjuvant capecitabine plus oxaliplatin (XELOX) versus control

BackgroundIn stage III colon cancer, oxaliplatin/5-fluorouracil (5-FU)-based adjuvant chemotherapy (FOLFOX) improves disease-free survival (DFS) and overall survival (OS). In rectal adenocarcinoma following neoadjuvant chemoradiation (CRT), we examined the benefit of postoperative adjuvant capecitabine and oxaliplatin (XELOX) chemotherapy.MethodsEligible patients were randomly assigned following fluoropyrimidine-based CRT and curative resection to observation or six cycles of XELOX. The primary end point was DFS; secondary end points were acute toxicity and OS. 390 patients were required in each arm, to detect an improvement in 3-year DFS from 40% to 50.5%, with 85% power and two-sided 5% significance level.ResultsThe study closed prematurely in 2008 because of poor accrual. Only 113 patients were randomly assigned to either observation (n = 59) or XELOX (n = 54). Compliance was poor, 93% allocated chemotherapy started and 48% completed six cycles. Protocolised dose reductions in XELOX were 39%, and levels of G3/G4 toxicity 40%. After a median follow-up of 44.8 months, 16 patients (27%) in the observation arm had relapsed or died compared with 12 patients (22%) in XELOX. The 3-year DFS rate was 78% with XELOX and 71% with observation [hazard ratio (HR) for DFS = 0.80; 95% confidence interval (CI) 0.38–1.69; P = 0.56]. The 3-year OS for XELOX and observation were 89% and 88%, respectively (HR for OS = 1.18; 95% CI 0.43–3.26; P = 0.75).ConclusionsThe observed improvement in DFS for adjuvant XELOX and similar OS were not statistically significant, as expected given the small number of patients and consequent low power. Our findings support the need for trials that test the role of neoadjuvant chemotherapy.ClinicalTrials.gov IdentifierNCT00427713.     

The role of neoadjuvant chemotherapy in ovarian cancer

Introduction: Ovarian cancer is mostly diagnosed at advanced stage. Better survival is achieved through complete debulking surgery and chemotherapy. Historically, neoadjuvant chemotherapy (NAC) has been introduced for unresectable disease to decrease tumor load and perform a unique complete surgery. Four randomized control trials have compared primary debulking surgery to NAC, but there is still controversy about the use of neoadjuvant chemotherapy and questions about its modalities.

Areas covered: We made a review of knowledge on benefits of NAC compared to primary debulking chemotherapy, in terms of survival and morbidity, methods of administration, new drugs in early and late phase trials, the selection of patients. Similar survival was observed after NAC and interval debulking surgery or primary debulking surgery. Morbidity of surgery was decreased after interval debulking compared primary debulking surgery. Conventional drugs are carboplatin and paclitaxel. Safety of bevacizumab was evaluated in phase 2 trials associated with conventional drugs. Immunotherapy trials are enrolling patients in phase 1 study.

Expert commentary: NAC followed by debulking surgery is the best treatment for patients with advanced ovarian cancer.     

Ⅳ期非小细胞肺癌化疗同期胸部三维放疗的前瞻性临床研究(一)——疗效与不良反应

目的 研究Ⅳ期非小细胞肺癌(NSCLC)化疗同期胸内病灶三维放疗的疗效和安全性.方法 2003-2010年共入组201例,可疗效分析182例,安全性分析201例.化疗以铂类为基础二药联合方案,中位周期数为4个.胸内病灶中位计划靶体积剂量为63 Gy.分析患者的生存情况,胃肠道、血液学不良反应,放射性肺炎和食管炎.用Kaplan-Meier法进行生存分析,Cox回归模型进行多因素分析.结果 201例的随访率为97.5％,随访满＜1、1～2、≥3年者分别为201、170、134例.全组182例中4～5个周期化疗同期三维放疗和同期三维放疗≥63 Gy的1、2、3年生存率以及中位生存期(MST)分别为54％和66％、20％和23％、13％和19％以及14.3个月和16.1个月;相似放化疗强度下单器官和多器官转移的MST分别为13.0个月和8.5个月(x2=10.10,P=0.001);同期放疗≥63 Gy 和＜63 Gy的MST在全组、4～5个周期化疗的分别为14.9个月和8.4个月(x2=20.48,P=0.000)、16.1个月和8.8个月(x2 =11.75,P=0.001),单器官、多器官的分别为16.0个月和9.0个月(x2=10.51,P=0.001)、11.0个月和7.0个月(x2=7.90,P=0.005).多因素分析显示4～5个周期化疗同期放疗≥63 Gy(β=0.243,P=0.019)、治疗后卡氏评分变化(β=1.268,P=0.000)对生存有影响.201例患者的2+3级胃肠反应发生率为45.0％;3+4级白细胞、血小板、血红蛋白不良反应发生率分别为35.0％、18.0％、15.0％;2+3级放射性肺炎和食管炎发生率分别为9.5％和13.4％.结论 Ⅳ期NSCLC化疗同期原发灶高剂量三维放疗可能使生存期延长,不良反应可接受.     

Metastatic Squamous Cell Carcinoma of an Unknown Primary Tumor Localized to the Neck

68 patients with metastatic squamous-cell carcinoma (SCC) of an unknown primary tumor localized to the neck were treated between 1981 and 1990. There were 11 patients treated with radiotherapy alone, 24 patients treated with surgery and radiotherapy and 33 patients treated with radiotherapy and chemotherapy. Male to female ratio was 1.9 : 1 and the median age was 55 years (range, 33 to 71 years). 41 (61%) patients had N3 disease, 18 (26%) patients had N2 disease and 9 (13%) patients had N1 disease. The majority of N3 patients were treated with radiotherapy + chemotherapy (n=17) and surgery + radiotherapy (n=17). The complete response (CR) to radiotherapy + chemotherapy was 73% with 19 patients having no evidence of disease currently. The median survival time (MST of this group was 34+ months. Of the 35 patients who had surgery and/or radiotherapy, 7 (20%) currently have no evident disease. The MST of these two groups (combined) was 22 months. Patients with N3 disease who received radiotherapy + chemotherapy had a higher CR rate and longer MST when compared with those without chemotherapy.     

Impact of neoadjuvant chemotherapy on the survival of patients with stage IIIc and IV epithelial ovarian cancer

OBJECTIVE: To compare the survival of patients with stage IIc or IV epithelial ovarian cancer treated either with neoadjuvant chemotherapy (NAC) followed by cytoreductive surgery or primary cytoreductive surgery (PCS) followed by adjuvant chemotherapy. METHODS: The clinical and pathological data of 160 patients with stage IIIc or IV epithelial ovarian cancer diagnosed pathologically between 1997 and 2005 were retrospectively reviewed. Forty-two patients were treated with NAC followed by cytoreductive surgery (NAC group) and 118 patients with PCS followed by adjuvant chemotherapy (PCA group). RESULTS: The overall response rate of NAC group was 69.1%. No significant difference was observed between the NAC group and PCS group in operating time, intra-operative blood loss and units of blood-transfusion (P > 0.05). Optimal cytoreductive surgery was performed in 88.1% of NAC group versus in 71.2% of PCS group (P < 0.05). In those who had optimal cytoreductive surgery, the recurrent rate was 43.2% in NAC group versus 56.0% in PCS group without significant difference between two groups (P > 0.05). The disease-free survival and progression-free survival was 7 and 8 months in NAC group, which were significantly shorter than 13 and 18 months in PCS group (P < 0.05), however, the median overall survival (OS) was 34 months in NAC group versus 43 months in PCS group without significant difference (P > 0.05). In the patients with optimal cytoreductive surgery, it was 34 months in NAC group versus 48 months in PCS group without significant difference either between two groups (P > 0.05). CONCLUSION: Neoadjuvant chemotherapy followed by cytoreductive surgery can improve the rate of optimal cytoreductive surgery for the patients with stage IIIc or IVepithelial ovarian cancer, but this regimen may neither reduce the recurrent rate nor prolong the survival when compared with the patients treated with primary cytoreductive surgery followed by adjuvant chemotherapy.     

Gemcitabine and vinorelbine followed by weekly docetaxel in patients with advanced non-small-cell lung cancer: a phase II trial of sequential chemotherapy

Objective We conducted this phase II trial to evaluate the efficacy and toxicity of the sequential nonplatinum combination chemotherapy consisting of gemcitabine (GEM) and vinorelbine (VNR) followed by weekly docetaxel (DOC) in patients with advanced non-small-cell lung cancer (NSCLC). Patients and methods Eligibility criteria: stage IV NSCLC, Performance status ≤2, adequate renal, hepatic and bone marrow function. Treatment consisted on: VNR 25 mg/m² plus gemcitabine 1000 mg/m², on days 1 and 8 of each 21-day cycle, followed by docetaxel 36 mg/m² weekly until progression or unacceptable toxicity. Results 21 stage IV patients were enrolled. All patients are evaluable for treatment response and toxicity profile. The mean age of the patients was 63 years (range: 51 to 72) with 18 (86%) males and 3 (14%) females. Histology types were: adenocarcinoma in 8 patients (38%), large cell carcinoma in 1 patients (5%) and squamous cell carcinoma in 12 patients (57%). The majority of the patients had and ECOG PS of 1. Eight patients (38%) did not complete six cycles of gemcitabine-navelbine. The median number of cycles of gemcitabine-navelbine was 4 (range 2–6). Of the 13 patients (61%) who completed six cycles of gemcitabine-navelbine, all of them went on to receive weekly docetaxel and received at least 3 cycles, with a median number of 8 cycles (range 3–16). The overall response rate was 33%. Respect survival, the minimum follow-up was 6 months (range, 6–25 months). The median survival time (MST) was 7.9 months, and the 1-year survival was 30%, and the median progression-free survival was 4.7 months. Toxicity was mild, well tolerated and mostly hematologic. In the GEM/VNR cycle, grade 3/4 neutropenia occurred in 14%, two patients with febrile neutropenia. Grade 3 anaemia in 1 patients (5%) and grade 3 thrombocytopenia in 1 patient (5%). Nonhematologic toxicity was also mild: 1 patient with Grade 3 skin toxicity with docetaxel, 1 patient with grade 3 infection, 2 patients with grade 3 astenia and 1 patient with a mild allergic reaction postchemotherapy treatment with docetaxel. Conclusion The sequential triplet nonplatinum chemotherapy consisted of GEM/VNR followed by weekly DOC is active and can be administered safely in advanced NSCLC. Our results are similar with other sequential regimens and did not represent a significant improvement in the treatment of this disease.     

Neoadjuvant FOLFIRINOX followed by Chemoradiotherapy for Middle and Lower Rectal Cancer

Objective: Neoadjuvant concomitant chemoradiotherapy followed by surgical resection is the standard of care in the treatment of rectal cancer. We are investigating the value of adding combination chemotherapy oxaliplatin, irinotecan, leucovorin and fluorouracil (FOLFIRINOX) before neoadjuvant chemoradiotherapy. Methods: Forty-one patients with middle and lower rectal cancer were included. FOLFORINOX were given every 2 weeks over 2 months (4 cycles) followed by concomitant chemoradiotherapy (CRT). Surgery was done 6-8 weeks after CRT and then adjuvant 4 months of FOLFOX or XELOX were given. The primary end point was sphincter preservation rate. Results: All patients received the four cycles of neoadjuvant chemotherapy FOLFORINOX, 38 patients completed CRT and only 29 patients underwent surgery. 32 patients were available for assessment (29 patients who underwent surgery and three patients who refuse surgery because of no evidence of disease by endoscopy, imaging and biopsy). Sphincter preservation was achieved in twenty-one patients (51.2%). Pathological complete response rate was 24.1%. After a median follow up of 24 months. Median PFS was 20 months and 2-years PFS was 62.3%. The median overall survival of all patients was not reached, while 2-years OS was 76.5%. Conclusion: Neoadjuvant FOLFIRINOX followed by CRT for middle and lower rectal cancer is feasible, tolerable with satisfactory sphincter preservation rate.     

Capecitabine in combination with Oxaliplatin (XELOX) as a first-line therapy for advanced gastric cancer

Purpose We evaluated efficacy and safety of XELOX in previously untreated patients with AGC. Patients and methods Patients received intravenous oxaliplatin 130 mg/m² over 2 h on day 1 plus oral capecitabine 1,000 mg/m² twice daily on days 1–14, every 3 weeks (XELOX). Treatment was continued until disease progression, intolerable toxicities or eight cycles reached. All tumour evaluations were reviewed and confirmed centrally. Design was according to Ensign’s three-stage method. Results Fifty-four patients (37 men) were enrolled; median age 57 years (range 29–70). In total, 311 cycles of XELOX were delivered. Overall response rate was 63% (95% CI, 50–76%), with 3 complete and 31 partial responses. At 13 months’ median follow-up, median progression-free and overall survival were 5.8 (95% CI, 4.4–7.2) and 11.9 months (95% CI, 8.8–15.1), respectively. The most common haematological adverse event was anaemia (70% of patients). Grade 3–4 neutropenia was observed in four patients, with neutropenic fever in only one patient. Most common non-haematological toxicities were neuropathy (70%), vomiting (50%), diarrhoea (33%), and hand-foot syndrome (HFS) (39%). Grade 3–4 toxicities were rare. Treatment was delayed or the dose reduced in 30 and 15% of cycles, respectively. There was one treatment-related death associated with grade 4 neutropenic sepsis. Conclusion XELOX was active and well tolerated as a first-line therapy for AGC.     

Capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/folinic acid plus oxaliplatin (FOLFOX-4) as second-line therapy in metastatic colorectal cancer: a randomized phase III noninferiority study

BackgroundTo demonstrate the noninferiority of capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/folinic acid and oxaliplatin (FOLFOX-4) as second-line therapy in patients with metastatic colorectal cancer after prior irinotecan-based chemotherapy.Patients and methodsA total of 627 patients were randomly assigned to receive XELOX (n = 313) or FOLFOX-4 (n = 314) following disease progression/recurrence or intolerance to irinotecan-based chemotherapy. The primary end point was progression-free survival (PFS).ResultsPFS for XELOX was noninferior to FOLFOX-4 [hazard ratio (HR) = 0.97; 95% confidence interval (CI) 0.83–1.14] in the intention-to-treat (ITT) population. Median PFS was 4.7 months with XELOX versus 4.8 months with FOLFOX-4. The robustness of the primary analysis was supported by multivariate and subgroup analyses. Median overall survival in the ITT population was 11.9 months with XELOX versus 12.5 months with FOLFOX-4 (HR = 1.02; 95% CI 0.86–1.21). Treatment-related grade 3/4 adverse events occurred in 50% of XELOX- and 65% of FOLFOX-4-treated patients. Whereas grade 3/4 neutropenia (35% versus 5% with XELOX) and febrile neutropenia (4% versus < 1%) were more common with FOLFOX-4, grade 3/4 diarrhea (19% versus 5% with FOLFOX-4) and grade 3 hand–foot syndrome (4% versus < 1%) were more common with XELOX.ConclusionXELOX is noninferior to FOLFOX-4 when administered as second-line treatment in patients with metastatic colorectal cancer.     

改良DCF方案与XELOX方案一线治疗晚期胃癌的临床观察

目的:观察改良DCF方案与XELOX方案一线治疗晚期胃癌的临床疗效和安全性。方法:收集2010年10至2013年7月收治的65例初治晚期胃癌患者,其中41例应用改良DCF方案和24例应用XELOX方案。改良DCF方案为多西他赛60mg/m2静滴,d1;顺铂15mg/m2 静滴,d1～5;氟尿嘧啶375mg/m2静滴,d1～5,21天为1周期。XELOX方案为奥沙利铂130mg/m2静滴,d1;卡培他滨 1250mg/m2,分2次口服,d1～14,21天为1周期。化疗2个周期后按照RECIST 1.1标准评价疗效,按NCI CTC 3.0版评价毒副反应并随访生存情况。结果:65例患者均可评价疗效。改良DCF方案和XELOX方案的有效率（RR）分别为34.1%和33.3%,疾病控制率（DCR）分别为75.6%和70.8%,中位无进展生存期（PFS）分别为7.6个月和7.2个月,中位生存时间（OS）分别为11.9个月和11.5个月,以上差异均无统计学意义（P＞0.05）。两组不良反应均可耐受,主要表现为骨髓抑制、乏力、消化道反应,以I-II级为主,III-IV级较少;但DCF组白细胞下降和乏力发生率高于XELOX组(P＜0.05）,XELOX组周围神经毒性和手足综合征发生率高于DCF组(P＜0.05）。结论:改良DCF方案与XELOX方案一线治疗晚期胃癌的疗效相近,毒副反应可耐受,临床上可根据患者年龄、体力状况及其他因素个体化选择化疗方案。     

Phase II study of short-course capecitabine plus oxaliplatin (XELOX) followed by maintenance capecitabine in advanced colorectal cancer: XelQuali study

Purpose

To evaluate the efficacy, safety and quality of life of a short course of oxaliplatin plus capecitabine (XELOX) followed by single-agent capecitabine in patients with previously untreated, inoperable, metastatic colorectal cancer.

Methods

Patients received intravenous oxaliplatin 130?mg/m² on d1 plus oral capecitabine 1,000?mg/m² twice daily (bid) on d1?C14 every 21?days for four cycles. Patients achieving stable disease (SD) or better than received capecitabine 1,250?mg/m² bid on d1?C14 every 21?days until disease progression. The primary endpoint was progression-free survival (PFS).

Results

Overall, 21/45 (47%) of patients responded to the initial XELOX chemotherapy whilst SD or better was documented in 76%. Median PFS was 6.7 (95% CI 5.7?C9.6) months, and median overall survival (OS) was 20.5 (95% CI 13.1?C28.1) months. In the 34 patients who then received capecitabine maintenance therapy, the median PFS was 8.1 (95% CI 6.2?C11.8) months and median OS was 23.1 (95% CI 17.8?C28.5) months. A marked reduction in the vast majority of all grades of adverse event occurred on switching from initial XELOX to maintenance capecitabine chemotherapy including grades 1?C2 (77 vs. 47%) and grade 3 (7 vs. 3%) neuropathy, diarrhoea and lethargy.

Conclusions

Short-course XELOX followed by capecitabine maintenance therapy provides an active and well-tolerated treatment option for patients with previously untreated metastatic colorectal cancer. A median OS of more than 20?months is promising and by limiting the number of oxaliplatin infusions, this approach minimises the risk of unwanted cumulative neurotoxicity, is cheaper and more convenient for both patients and healthcare providers.     

Hyperthermic intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis: A multicenter propensity score-matched cohort study

ObjectiveSystemic chemotherapy has limited efficacy in the treatment of peritoneal metastasis (PM) in gastric cancer (GC). Hyperthermic intraperitoneal chemotherapy (HIPEC) combined with complete cytoreductive surgery (CRS) has shown promising outcomes but remains controversial. The present study aimed to evaluate the safety and efficacy of HIPEC without CRS in GC patients with PM.MethodsThis retrospective propensity score-matched multicenter cohort study included GC patients with PM treated with either chemotherapy alone (Cx group) or with HIPEC combined with chemotherapy (HIPEC-Cx group) in four Chinese high-volume gastric medical centers between 2010 and 2017. The primary outcomes were median survival time (MST) and 3-year overall survival (OS). Propensity score matching was performed to compensate for controlling potential confounding effects and selection bias.ResultsOf 663 eligible patients, 498 were matched. The MST in the Cx and HIPEC-Cx groups was 10.8 and 15.9 months, respectively [hazard ratio (HR)=0.71, 95% confidence interval (95% CI), 0.58−0.88; P=0.002]. The 3-year OS rate was 10.1% (95% CI, 5.4%−14.8%) and 18.4% (95% CI, 12.3%−24.5%) in the Cx and HIPEC-Cx groups, respectively (P=0.017). The complication rates were comparable. The time to first flatus and length of hospital stay for patients undergoing HIPEC combined with chemotherapy was longer than that of chemotherapy alone (4.6±2.4 dvs. 2.7±1.8 d, P<0.001; 14.2±5.8 dvs. 11.4±7.7 d, P<0.001), respectively. The median follow-up period was 33.2 months. ConclusionsCompared with standard systemic chemotherapy, HIPEC combined with chemotherapy revealed a statistically significant survival benefit for GC patients with PM, without compromising patient safety.     

Pathological response and outcome after neoadjuvant chemotherapy with DOC (docetaxel,oxaliplatin, capecitabine) or EOF (epirubicin,oxaliplatin, 5-fluorouracil) for clinical T3-T4 non-metastatic gastric cancer

PurposeIn this prospective observational study, we sought to compare the efficacy and safety of docetaxel + oxaliplatin + capecitabine (DOC) with epirubicin + oxaliplatin + 5-fluouracil (EOF) as neoadjuvant chemotherapy (NAC) for clinical T3 or T4 non-metastatic gastric cancer (GC) patients.MethodsThe DOC NAC consisted of docetaxel 35 mg/m² (days 1–8), oxaliplatin 85 mg/m² (day 1), and capecitabine 750 mg/m² twice daily (days 1–14), every 3 weeks. The EOF NAC consisted of intravenous (IV) epirubicin 50 mg/m2 combined with IV oxaliplatin 130 mg/m2 on day 1 and continuous infusion 5-fluouracil 750 mg/m2 on days 1–5, every 3 weeks. After 4 cycles of NAC or upon progression during chemotherapy, patients underwent gastrectomy with standard D2 or D3 lymphadenectomy. Pathological complete response rate per Becker tumor regression grading system was the primary endpoint and the secondary endpoints included progression-free survival (2-yr PFS) and 2-year overall survival (2-yr OS) and tolerability.ResultsOverall, we identified 63 patients with T3-4 non-metastatic GC starting either NAC regimen between January 2010 and December 2017 at our Institution: 34 in the DOC group and 29 in EOF group. Thirty patients (88%) in the DOC group and 22 (76%) in the EOF group completed the 4 planned cycles of NAC. Fifty-seven patients received surgery. Results indicated no statistical significant differences between the two groups, and only a trend for some better data in favour of the DOC group. The R0 resection rate was 90.6% and 88.0% for the DOC and EOF cohorts, respectively. The pathological complete response rate was 6.2% in the DOC group and 4.0% in the EOF group. Becker 1–2 pathological response was found in 46.8% of the DOC cohort and 28.0% of the EOF cohort (p = .14). The 2-yr PFS rate was 54.1% for DOC vs. 41.4% for EOF (p = .14) and the 2-yr OS rate was 80.8% for DOC vs. 58.6% for EOF (p = .05). Neutropenia was the most common grade ≥3 toxicity and occurred in 8 (23.5%) patients of the DOC group and 10 (34.4%) patients of the EOF group (p = .33).ConclusionsThese findings seem to confirm the feasibility of NAC for clinically T3 and T4 non-metastatic GC and, despite no statistical significant difference was documented, suggest a trend for better activity and tolerability for the docetaxel-based regimen (DOC) compared to the epirubicin-based combination (EOF).     

Phase II study of gemcitabine-cisplatin-paclitaxel triplet as induction chemotherapy in inoperable, locally-advanced non-small cell lung cancer

PURPOSE: Our objective was to determine the activity in terms of response rate, surgical resectability, and the tolerability of the new three-drug combination gemcitabine-cisplatin-paclitaxel (GCP) in unresectable stage IIIA(N2) and IIIB non-small cell lung cancer (NSCLC). PATIENT AND METHODS: Forty-two chemo-naive patients with stage IIIA(N2)-IIIB NSCLC, median age of 59 years, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and the ability to tolerate pneumectomy, received gemcitabine (Gem) 1000 mg/m(2) IV days 1 and 8, cisplatin (CDDP) 50 mg/m(2) IV days 1 and 8, paclitaxel 125 mg/m(2) 1h infusion IV days 1 and 8, every 21 days for 3 cycles. After induction chemotherapy, patients were evaluated for surgery or definitive radiotherapy. RESULTS: Grade 3-4 neutropenia was the main hematologic toxicity, occurring in 28% of patients. Grade 3-4 thrombocytopenia was observed in only 11% of cases. No neutropenic fever or bleeding episodes were recorded. Severe non-hematologic toxicity was uncommon. Thirty (71%, 95% CI: 57.2-84.7%) of the 42 eligible patients had objective responses (1 complete and 29 partial responses). After induction chemotherapy, 21 patients (50%) went to surgery. Complete resection was obtained in 16 patients (38%). Viable tumor was present in 18 of 21 resection specimens. In three cases only necrotic tumor cells were identified, for a pathological complete response of 7%. With a median follow-up of 13.9 months, median time to progression was 17.4 months, median survival 21.7 months and estimated 1-year survival 92%. CONCLUSIONS: GCP combination is active and well tolerated in locally-advanced, non-resectable NSCLC. The activity profile, in terms of response and surgical resection rate, is comparable to that obtained with standard doublets.