A triplet chemotherapy regimen of cisplatin,fluorouracil and paclitaxel for locoregionally recurrent nasopharyngeal carcinoma cases contraindicated for re-irradiation/surgery

Objective: Salvage treatment for locoregionally recurrent nasopharyngeal carcinoma remains a significant challenge. The present study was conducted to evaluate the efficacy, toxicity and prognostic factors of a triplet chemotherapy regimen involving cisplatin, fluorouracil and paclitaxel (TPF) for locoregionally recurrent nasopharyngeal carcinoma (NPC) cases contraindicated for re-irradiation/surgery.

Methods: Patients with locoregionally recurrent NPC unsuitable for re-irradiation/surgery were treated with TPF therapy. The chemotherapy drugs were administered as follows: 135 mg/m² paclitaxel on day 1, 25 mg/m²/day cisplatin on days 1–3, followed by continuously infused intravenous fluorouracil for 120 h at a variable dosage from 600 to 800 mg/m²/day, depending on prior radiation.

Results: Twenty-seven patients were enrolled. The overall response was 66.7%. The median progression-free survival (PFS) and overall survival (OS) were 8.5 and 27.2 months, respectively. Toxicity was mild to moderate. Neutropenia and leukopenia were the primary grade 3–4 chemotherapy toxicities. 6 patients who regained the potential for re-radiotherapy or surgery showed significantly better outcomes than those treated with chemotherapy alone (median PFS: 20.8 vs. 7.1 months, P = 0.005; median OS: 54.2 vs. 20.6 months, P = 0.021).

Conclusion: TPF triplet chemotherapy showed a high response rate for locoregionally recurrent NPC with an acceptable toxicity profile.     

Adjuvant docetaxel and carboplatin chemotherapy administered alone or with radiotherapy in a “sandwich” protocol in patients with advanced endometrial cancer: a single-institution experience

Objective: To evaluate the outcomes of adjuvant chemotherapy administered alone or with radiotherapy in a “sandwich” protocol in patients with advanced endometrial cancer.

Methods: The authors retrospectively reviewed the clinical records of patients with staged III – IV disease who received adjuvant chemotherapy (docetaxel plus carboplatin) administered alone or interposed with radiotherapy between January 2004 and August 2010.

Results: Of the 35 study patients, 10 (28.6%) had stage IIIA disease, 15 (42.9%) had IIIC1 disease, 7 (20.0%) had IIIC2 disease and 3 (8.6%) had IVB disease. Nine (90.0%) of the 10 patients with stage IIIA disease received four to six cycles of adjuvant docetaxel and carboplatin chemotherapy alone. All 25 patients with stage IIIC – IVB disease and 1 patient with stage IIIA disease received radiotherapy sandwiched between chemotherapy cycles (total, three to six cycles). The 3-year progression-free survival (PFS) and overall survival (OS) rates were 73.0 and 87.0%, respectively, for all patients. For patients with stage IIIC – IVB disease, the 3-year PFS and OS rates were 62.4 and 81.8%, respectively.

Conclusion: Combination chemotherapy with docetaxel and carboplatin interposed with radiotherapy is efficacious and well tolerated for stage IIIC – IVB endometrial cancer. Adjuvant chemotherapy alone with docetaxel and carboplatin might be sufficient for stage IIIA disease.     

Neoadjuvant docetaxel combined with cisplatin and followed by radical surgery for the treatment of locally advanced (stage IB2 – IIB) cervical cancer: preliminary results of a single-institution experience

Objectives: We aimed to determine the efficacy and toxicity of treating locally advanced cervical cancer (LACC) with a neoadjuvant chemotherapy (NAC) regimen combining docetaxel and cisplatin followed by radical surgery.

Methods: We retrospectively reviewed the clinical records of patients with stage IB2 – IIB (tumor diameter ≥ 4 cm) disease admitted between January 2007 and July 2009 who, before radical hysterectomy and pelvic lymph node dissection, received two to three courses of an NAC regimen comprising docetaxel (75 mg/m²) and cisplatin (70 – 75 mg/m²).

Results: Fifty-two patients with LACC received 109 cycles of NAC. The objective response rate was 86.5% (26.9% CR and 17.3% pathological CR). Stage IB2 disease had a more favorable response to NAC (95.7%, p = 0.019). Deep stromal invasion and lymph-vascular space metastasis rates were significantly lower in NAC responders (p = 0.033) than in nonresponders (p = 0.012). Most side effects of NAC were mild or moderate. Log-rank test showed the 2-year overall survival and progression-free survival rates were 100 and 90.3% for NAC responders, compared with only 57.1% (p = 0.000) and 68.6% for nonresponders (p = 0.012), respectively.

Conclusion: Neoadjuvant docetaxel combined with cisplatin yielded a high response rate with well tolerable toxicity for LACC and could decrease pathological risk factors in NAC responders.     

First-line bevacizumab,cisplatin and vinorelbine plus maintenance bevacizumab in advanced non-squamous non-small cell lung cancer chemo-naïve patients

Objective: The aim of this study was to evaluate efficacy and safety of first-line treatment with bevacizumab, cisplatin and vinorelbine and bevacizumab maintenance in non-squamous, non-small cell lung cancer (NSCLC).

Research design and methods: Forty-nine patients with stage IIIB plus pleural effusion or stage IV NSCLC were included in a Phase II clinical trial. Treatment consisted of 3-week cycles of bevacizumab (15 mg/kg on day 1), cisplatin (80 mg/m² on day 1) and vinorelbine (25 mg/m² on days 1 and 8). After 6 cycles, non-progressing patients received bevacizumab maintenance therapy. The primary end point was progression-free survival (PFS), calculated using the Kaplan–Meier method.

Results: Thirteen (29%) of 45 evaluable patients presented a partial response. PFS and overall survival were 6.0 months (95% confidence interval (CI) 4.5 – 7.5) and 14.7 months (95% CI 8.4 – 21), respectively. Fourteen patients (28%) experienced grade 3 – 4 neutropenia and 7 (14%) experienced febrile neutropenia during the combination treatment. During the maintenance phase, the most frequent grade 3 – 4 adverse event was hypertension. Neither grade 3 – 4 thrombocytopenia nor toxic death was observed.

Conclusions: The studied regimen achieved a similar efficacy to other regimens containing platinum doublets. The data provide further evidence that bevacizumab may be used in combination with multiple standard platinum-based doublets in this setting.     

The value of surrogate endpoints for predicting real-world survival across five cancer types

Objective It is unclear how well different outcome measures in randomized controlled trials (RCTs) perform in predicting real-world cancer survival. We assess the ability of RCT overall survival (OS) and surrogate endpoints – progression-free survival (PFS) and time to progression (TTP) – to predict real-world OS across five cancers.

Methods We identified 20 treatments and 31 indications for breast, colorectal, lung, ovarian, and pancreatic cancer that had a phase III RCT reporting median OS and median PFS or TTP. Median real-world OS was determined using a Kaplan–Meier estimator applied to patients in the Surveillance and Epidemiology End Results (SEER)-Medicare database (1991–2010). Performance of RCT OS and PFS/TTP in predicting real-world OS was measured using t-tests, median absolute prediction error, and R² from linear regressions.

Results Among 72,600 SEER-Medicare patients similar to RCT participants, median survival was 5.9 months for trial surrogates, 14.1 months for trial OS, and 13.4 months for real-world OS. For this sample, regression models using clinical trial OS and trial surrogates as independent variables predicted real-world OS significantly better than models using surrogates alone (P?=?0.026). Among all real-world patients using sample treatments (N?=?309,182), however, adding trial OS did not improve predictive power over predictions based on surrogates alone (P?=?0.194). Results were qualitatively similar using median absolute prediction error and R² metrics.

Conclusions Among the five tumor types investigated, trial OS and surrogates were each independently valuable in predicting real-world OS outcomes for patients similar to trial participants. In broader real-world populations, however, trial OS added little incremental value over surrogates alone.     

Safety and efficacy of single-day GemOx regimen in patients with pancreatobiliary cancer: a single institution experience

Background: GemOx (gemcitabine 1000 mg/m² >?100 min on day 1 and oxaliplatin 100 mg/m² on day 2 every 2 weeks) achieved a response rate of 26.8%, improved progression-free survival (PFS) but failed to demonstrate a benefit in overall survival (OS) compared with gemcitabine in pancreatic cancer. This regimen has regained attention after recent pooled- and meta-analysis suggested a survival benefit of gemcitabine–platinum doublets over gemcitabine. However, GemOx is associated with inconvenience to patients, early cumulative dose developing neuropathy and thrombocytopenia. In addition, fixed dose rate of gemcitabine showed no benefit >?30 min infusion schedule in the ECOG6201 study. Pharmacokinetic profiles of both drugs did not show statistically significant difference regardless of the order of administration.

Patients and methods: In order to create a more convenient and equally effective regimen, we conducted a retrospective study to evaluate the efficacy and safety of single-day modified GemOx (S-GemOx, gemcitabine 1000 mg/m² >?30 min and oxaliplatin 85 mg/m² >?2 h on day 1 every 2 weeks) in patients with pancreatic and biliary cancers.

Results: In all, 34 patients (median age 60 years, male/female: 17/17) received S-GemOx including locally advanced or metastatic pancreatic cancer (26) and biliary duct carcinoma (8). Median treatment was six cycles with duration of 12 weeks (range (r): 2 – 56). Median cumulative dose of oxaliplatin was 517.5 mg/m² (r: 85 – 2380). A total of 27 of 34 patients were evaluated for efficacy after initial staging: 1 (3.7%) complete response (CR), 4 (14.8%) partial response (PR), 18 (66.7%) stable disease and 4 (14.8%) progression of disease. Overall response rate (CR + PR) was 18.5%. Median PFS and OS were 7 and 11.6 months, respectively. All patients were assessed for toxicities. Grade 3/4 hematological toxicities include anemia (8%), neutropenia (11%), thrombocytopenia (5%), nausea/vomiting (3%), diarrhea (3%), hypersensitivity reaction (14%) and neuropathy (3%). No deaths occurred due to therapy.

Conclusions: S-GemOx regimen provides convenient schedule, toxicities appear to be comparable with GemOx. The incidence of neuropathy (3 vs 19.1%) and thrombocytopenia (5 vs 14%) are substantially lower compared with GemOx. Prospective studies of S-GemOx in a large patient population are warranted.     

Pixantrone,etoposide, bendamustine,rituximab (P[R]EBEN) as an effective salvage regimen for relapsed/refractory aggressive non-Hodgkin lymphoma—Polish Lymphoma Research Group real-life analysis

BackgroundDespite a significant improvement in treatment outcomes, 30–40% of aggressive non-Hodgkin lymphomas (NHL) patients are refractory or relapse after the first line therapy. Half of them are not eligible to autologous stem cell transplantation (ASCT) due to failure of platinum-based salvage regimens. Pixantrone is conditionally approved in Europe in patients with R/R aggressive NHL failing at least 2 previous lines of therapy. Polish Lymphoma Research Group (PLRG) evaluated the efficacy and tolerability of P[R]EBEN combining pixantrone, etoposide, bendamustine with or without rituximab), a new regimen developed recently by Francesco d’Amore, in real-life experience.MethodsIn this retrospective audit, we analyzed the data of consecutive 25 R/R NHL cases, treated with P[R]EBEN regimen in 9 PLRG centers. Safety and efficacy data, including adverse reactions (AE), response rates, progression-free and overall survival (PFS and OS) were collected.ResultsOverall response rate (ORR) to P[R]EBEN regimen was 68% (40% CR and 28% PR). Most patients responded, relatively early, by second cycle of therapy. P[R]EBEN was effective in 8 out of 15 patients (53%) refractory to previous platinum-based salvage regimens. In 4 patients (16%) stabilization of disease (SD) during therapy was observed and further 4 patients (16%) progressed during the treatment (PD). Response rates were higher in patients, chemosensitive to their prior regimen (ORR – 87.5%, including 50% CR). At the median follow-up of 7.5 months (range 1–16) the median PFS and OS were not reached. Projected PFS and OS at 12 months are 68% and 78% respectively. The P[R]EBEN regimen was well tolerated and most of patients received it as out-patients. AEs grade ≥3 occurred in 17 patients (68%). Most common grade 3–4 AEs were due to hematological toxicity with febrile neutropenia observed in 5 patients (20%). There were no episodes of septic deaths. Six patients (24%) died during treatment and follow-up period, all of them due to lymphoma progression.ConclusionOur data suggest good efficiency and tolerability of P[R]EBEN regimen as a rescue therapy in patients with R/R aggressive NHL.     

8种胃癌化疗药物与药品不良反应的聚类关系分析

目的：分析胃癌化疗药物不良反应与药品品种间的聚类关系,促进临床安全合理用药。方法：收集109家药品生产企业2010-2014年生产的8种胃癌化疗药物氟尿嘧啶、卡培他滨、表柔比星、顺铂、伊立替康、紫杉醇、奥沙利铂和多西他赛的不良反应报告数据,运用数据挖掘技术对药品不良反应与药品品种间的关系进行聚类分析,使用Clementine 14.1软件进行统计。结果与结论：共收集有效报告10572份,卡培他滨和顺铂,表柔比星和伊立替康,多西他赛和紫杉醇联合用药发生一般药品不良反应的可能性较大。卡培他滨、顺铂、伊立替康和表柔比星联合用药;多西他赛、氟尿嘧啶和紫杉醇联合用药时,出现严重药品不良反应的概率较高。瘙痒、过敏性休克、顺铂、多西他赛在聚类过程中的运算比重较大。     

利妥昔单抗联合多柔比星脂质体治疗复发难治性非霍奇金淋巴瘤的疗效观察

目的探讨利妥昔单抗注射液联合多柔比星脂质体治疗复发难治性非霍奇金淋巴瘤的临床疗效和不良反应。方法选取2014年1月—2015年1月沧州市中心医院收治的复发难治性非霍奇金淋巴瘤患者60例为研究对象,所有患者随机分为对照组和治疗组,每组各30例。对照组静脉滴注盐酸多柔比星脂质体注射液,20 mg/m~2,1次/2周。治疗组在对照组的基础上静脉滴注利妥昔单抗注射液375 mg/m~2,1次/周。两组患者均连续治疗6周。观察两组的临床疗效,比较两组的无进展生存期(PFS)、总生存期(OS)和患者Karnofsky(KPS)评分。结果治疗后,对照组和治疗组的总有效率分别为36.67%、66.67%,疾病控制率分别为56.67%、80.00%,两组比较差异有统计学意义(P0.05)。治疗后,治疗组PFS、OS和KPS评分均显著高于对照组,两组比较差异有统计学意义(P0.05)。治疗组发生白细胞计数降低、贫血的例数显著低于对照组,两组比较差异有统计学意义(P0.05)。结论利妥昔单抗注射液联合多柔比星脂质体治疗复发难治性非霍奇金淋巴瘤具有较好的临床疗效,可延长患者生存时间,改善生活质量,安全性较好,具有一定的临床推广应用价值。     

Efficacy and safety of doublet versus single agent as salvage treatment for metastatic breast cancer pretreated with anthracyclines and taxanes: a systematic review and meta-analysis

Aim: To perform a systematic review and meta-analysis of randomized controlled trials to compare the efficacy and safety of doublet versus single agent as salvage treatment for pretreated metastatic breast cancer.

Methods: A comprehensive literature search was performed to identify relevant randomized controlled trials (RCTs). All clinical studies were independently identified by two authors for inclusion. Demographic data, treatment regimens, objective response rate (ORR), and progression-free survival (PFS) and overall survival (OS) were extracted and analyzed using Comprehensive MetaAnalysis software (Version 2.0).

Results: Thirteen RCTs involving 4878 pretreated metastatic breast cancer patients were ultimately identified. The pooled results demonstrated that doublet combination therapy significantly improved ORR (RR 1.13, 95% CI: 1.01–1.27, p?<?.001) and PFS (hazard ration [HR] 0.83, 95% CI: 0.73–0.96, p?=?.011), but not OS (HR 0.93, 95% CI: 0.86–1.01, p?=?.065). Similar results were observed in sub-group analysis according to treatment regimens. Additionally, more incidences of grade 3 or 4 myelosuppression toxicities nausea and fatigue were observed in doublet combination therapy.

Conclusions: In comparison with a single agent alone, doublet combination therapy as salvage treatment for pretreated metastatic breast cancer patients significantly improves ORR and PFS, but not OS. Further studies are recommended to identify patients who will most likely benefit from the appropriate doublet combination therapy.     

Modified docetaxel,cisplatin and fluorouracil therapy as the first-line treatment for patients with recurrent/metastatic squamous cell carcinoma of the head and neck cancer: a retrospective study

Aim: Modified docetaxel, cisplatin, and 5-fluorouracil (mDCF) therapy has been shown to be a well tolerated and highly effective regimen for metastatic gastric carcinoma. Herein we investigated the effectiveness of the mDCF combination as the first-line treatment in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (HNSCC).

Methods: A total of 80 patients with recurrent/metastatic HNSCC who were treated with mDCF between 2009 and 2015 were enrolled into this study. All patients were treated in the first-line with 2–6 cycles of mDCF chemotherapy which consisted of docetaxel 60?mg/m² intravenously (IV) on day 1, cisplatin 60?mg/m² IV on day 1, and 5-fluorouracil 600?mg/m² IV for 5 days of continuous infusion, with cycles repeated every 21 days.

Results: The most common grade 3–4 toxicities were neutropenia (22.5%), anemia (10%), thrombocytopenia (7.5%), nephrotoxicity (1.3%), hepatotoxicity (1.3%), and diarrhea (2.5%). Twelve patients (15%) experienced a febrile neutropenic episode. Dose modification was required in 22 (27.5%) of the patients due to drug toxicity. Complete response was achieved in 2.5% of all patients, while partial and stable responses were reported to be 43.8% and 25%, respectively, with a disease control rate of 71.3%. The median progression-free and overall survival was 7 (95% CI: 5.3–8.6) and 11.5 (95% CI: 9.4–13.7) months, respectively.

Conclusions: The efficiency of the mDCF combination for induction chemotherapy has been well established previously. To our knowledge, this is one of the largest studies evaluating the survival and safety significance of mDCF chemotherapy as a first-line treatment in patients with recurrent/metastatic HNSCC.     

Brentuximab Vedotin (SGN-35), an antibody–drug conjugate for the treatment of CD30-positive malignancies

Introduction: CD30-positive hematological malignancies are potentially curable with frontline combination chemotherapy regimens; however, those patients who relapse or are refractory to initial therapies have less favorable prognosis.

Areas covered: Brentuximab vedotin is an antibody–drug conjugate (ADC) composed of the anti-CD30 chimeric IgG1 monoclonal antibody cAC10 and the potent antimicrotubule drug monomethylauristatin E connected by a protease-cleavable linker. Treatment with single-agent brentuximab vedotin resulted in unprecedented objective response rates and complete response rates of 75 and 34%, respectively, in relapsed or refractory Hodgkin lymphoma, and of 86 and 57%, respectively, in relapsed or refractory systemic anaplastic large-cell lymphoma patients. Peripheral sensory neuropathy and neutropenia were observed with brentuximab vedotin but were generally grade 1 and 2 in severity and manageable. In August 2011, brentuximab vedotin was approved in the US for the treatment of Hodgkin lymphoma after failure of autologous stem cell transplant (ASCT) or after failure of at least two prior multiagent chemotherapy regimens in ASCT-ineligible candidates, and for the treatment of systemic anaplastic large-cell lymphoma after failure of at least one prior multiagent chemotherapy regimen.

Expert opinion: These data support an expanded development program for brentuximab vedotin in multiple CD30-positive indications.     

Sorafenib in locally advanced or metastatic breast cancer

Introduction: Sorafenib is an oral multikinase inhibitor with anti-angiogenic and anti-proliferative activity that is indicated for use in hepatocellular and renal cell carcinomas. Sorafenib is being developed in a number of solid tumors, including breast cancer (BC).

Areas covered: A series of four randomized, double-blind, placebo-controlled Phase IIb screening Trials were developed to Investigate the Efficacy of Sorafenib (TIES) when added to select chemotherapies for patients with HER2-negative advanced BC with a primary endpoint of progression-free survival (PFS). Results have been varied. SOLTI-0701 reported significant PFS benefit for sorafenib plus capecitabine as first- or second-line treatment, and AC01B07 reported a modest but significant PFS benefit when sorafenib was combined with gemcitabine or capecitabine for patients whose disease had progressed during or after bevacizumab. Sorafenib plus first-line paclitaxel did not significantly improve PFS (NU07B1 study), nor did its addition to first-line docetaxel and/or letrozole (FM-B07-01 study). A Phase III trial of sorafenib plus capecitabine has been initiated.

Expert opinion: Phase IIb data indicate a potential role for sorafenib in combination with select chemotherapies for HER2-negative advanced BC, but Phase III confirmatory trials are necessary. The variability in results across studies with sorafenib may be related to the chemotherapy combination and/or patient population.     

Small molecule dipeptidylpeptidase IV inhibitors under investigation for diabetes mellitus therapy

Importance of the field: Fluoropyrimidines with oxaliplatin or irinotecan, bevacizumab, cetuximab and panitumumab constitute the drugs currently approved by the FDA for the treatment of patients with metastatic colorectal cancer (mCRC). Patients who have progressed on the approved drugs pose a major challenge for medical oncologists, as the therapeutic choices outside the context of a clinical trial are limited.

Areas covered in this review: Mitomycin C is an old drug that acts synergistically with capecitabine and irinotecan. Relevant studies were identified in PubMed (years 1950 – 2009), Ovid, Cochrane database and the American Society of Clinical Oncology abstracts (years 1995 – 2009) using the following search terms: mitomycin C, fluorouracil, capecitabine, irinotecan, oxaliplatin, and colorectal cancer. Only studies using the combination of mitomycin C with one of the aforementioned agents were selected.

What the reader will gain: An overview of the clinical trials where mitomycin has been used in combination with modern compounds in the various settings of metastatic colorectal cancer.

Take home message: Mitomycin C combinations are less efficacious than modern drugs in the first-line treatment of colorectal cancer. However, they are acceptable alternatives for best supportive care in colorectal cancer that is refractory to standard regimens, as they show some modest efficacy at low cost.     

Comparative effectiveness of everolimus and axitinib as second targeted therapies for metastatic renal cell carcinoma in the US: a retrospective chart review

Background Second targeted therapies for metastatic renal cell carcinoma (mRCC) include mammalian target of rapamycin inhibitors (mTORis) and tyrosine kinase inhibitors (TKIs). This observational study compares overall survival (OS) and progression-free survival (PFS) of patients treated with everolimus (an mTORi) and axitinib (a TKI) following first TKI, and assesses the impact of type and duration of first TKI on the relative effectiveness of these second targeted therapies.

Methods Retrospective reviews of medical records were conducted by medical oncologists or hematologists/oncologists recruited from a nationwide panel. Included patients with mRCC were required to have discontinued a first TKI (sunitinib, sorafenib, or pazopanib) for medical reasons, and to have initiated everolimus or axitinib as second targeted therapy between February 2012 and January 2013. OS and PFS were compared between patients treated with everolimus vs. axitinib using multivariable Cox proportional hazards regression models. Comparative results were also stratified by type and duration of first TKI.

Results Included patients (n?=?325 for everolimus and n?=?127 for axitinib) had a mean age of 61 years and 31% were female. Sunitinib was the most commonly used first TKI (73%). After adjusting for patient characteristics, no statistically significant differences were observed in OS or PFS between everolimus and axitinib. When stratifying by type and duration of first TKI, there was no statistically significant difference in OS between everolimus and axitinib in all subgroups except for patients with?<6 months on sunitinib or sorafenib as first TKI. No significant difference in PFS was observed in any subgroup.

Limitations Important limitations include potential missing or inaccurate data in medical charts, and confounding due to unobserved factors.

Conclusions In this retrospective chart review, no significant differences were detected in OS or PFS between axitinib and everolimus as second targeted therapy. Longer duration of first TKI was not associated with increased effectiveness of subsequent axitinib compared to everolimus.     

A phase II trial of gefitinib in combination with capecitabine and oxaliplatin as first-line chemotherapy in patients with advanced colorectal cancer

ABSTRACT

Objective: This study was designed as a multicentre phase II trial to assess the efficacy and safety of gefitinib in association with capecitabine and oxaliplatin in patients with untreated metastatic colorectal cancer.

Research design and methods: Patients with metastatic colorectal cancer that had received no prior chemotherapy for advanced disease were treated with oral gefitinib (250?mg daily) plus oral capecitabine (1000?mg/m² twice a day on Days 1–14) and intravenous oxaliplatin (120?mg/m² on Day 1 of each 3?week cycle).

Results: Thirty-five patients were enrolled. In the intention-to-treat analysis, 3 (8.6%) patients experienced a complete response (CR), 14 (40%) a partial response (PR) and 11 (31.4%) had stable disease (SD). The disease control rate (CR + PR + SD) was 80%, the median time to progression was 7.3 months (95%CI: 4.76–9.2) and the estimated median overall survival was 21.9 months (95% CI: 15.1–not reached). The most common grade 3 to 4 toxicities included diarrhoea (31%) and vomiting (5.7%).

Conclusions: The combination of capecitabine, oxaliplatin and gefitinib appears to have promising activity in chemotherapy-naïve metastatic colorectal cancer. A higher disease control rate and an increase in median overall survival were seen compared with previous reports with capecitabine and oxaliplatin in similar patient populations. The tolerability profile appears to be predictable and similar to capecitabine/oxaliplatin regimens.     

Tirofiban: an investigational plateletglycoprotein IIb/IIIa receptor antagonist

Introduction: Fluoropyrimidines with oxaliplatin or irinotecan plus bevacizumab is the standard chemotherapy combination in patients with advanced colorectal cancer (CRC). Gemcitabine acts synergistically with fluoropyrimidines to enhance the binding of thymidylate synthase and increase inhibition of DNA synthesis. The objective of this review is to evaluate the literature for evidence of efficacy and safety of fluoropyrimidine plus gemcitabine (FG) in patients with advanced CRC. Methods: Relevant studies were identified in PubMed, Ovid, Cochrane database and the American Society of Clinical Oncology abstracts using the following search terms: gemcitabine, fluorouracil, capecitabine and colorectal cancer. Only studies using the FG combination were selected. Results: Forty-two advanced CRC patients were evaluated in two Phase I studies and the maximum tolerated dose of gemcitabine was 900 – 1,000 mg/m² weekly with either bolus 5-fluorouracil (5-FU) or capecitabine. A total of 216 advanced CRC patients were evaluated in six Phase II studies. Gemcitabine (750 – 1,250 mg/m²) with either 5-FU (continuous infusion or bolus) or capecitabine was administered as first-line therapy in two studies and as third-line therapy in three studies. The range reported for overall response rate was 30 – 38.3%, median time to progression was 4 – 8.3+ months and median survival was 9.8 – 18+ months. The most commonly reported grade 3 – 4 toxicities were neutropenia, thrombocytopenia and mucositis. Conclusions: Fluoropyrimidine plus gemcitabine is clinically active in patients with refractory CRC demonstrating prolonged median time to progression and acceptable toxicity only when bolus 5-FU was not used. Studies are underway to evaluate the combinations of FG with other chemotherapy or targeted agents. Meanwhile, FG may be considered for patients with advanced CRC who are refractory to primary treatment without other options or who are not eligible for clinical studies.     

复方苦参注射液联合ET方案治疗乳腺癌的临床研究

目的探讨复方苦参注射液联合ET方案(表柔比星联合多西他赛)治疗乳腺癌的临床疗效。方法选取2016年1月—2017年12月邳州市中医院收治的94例晚期乳腺癌患者作为研究对象,将所有患者随机分为对照组和治疗组。每组各47例。对照组患者给予ET方案治疗,静脉滴注注射用盐酸表柔比星70 mg/m~2,连续3 d,4周后重复1次;静脉滴注多西他赛注射液75mg/m~2,1次/周,连用6周,停2周。治疗组患者在对照组治疗的基础上第1～10天静脉滴注复方苦参注射液,20 mL用氯化钠注射液200 mL稀释。8周为1个疗程,两组患者均治疗2个疗程。观察两组近期临床疗效,比较两组患者的无进展生存期(PFS)、总生存期(OS)、生存质量测定量表简表(QOL-BREF)评分、肿瘤标志物和免疫因子水平。结果治疗后,对照组的临床缓解率为38.3%,疾病控制率为72.3%,分别显著低于治疗组的57.4%、89.4%,两组比较差异具有统计学意义(P0.05)。治疗后,治疗组患者的PFS、OS显著高于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,治疗组的QOL-BREF评分显著升高,同组比较差异具有统计学意义(P0.05),且治疗后治疗组QOL-BREF评分显著高于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组血清癌胚抗原(CEA)、糖类抗原153(CA153)和糖类抗原125(CA125)水平均显著降低,同组治疗前后比较差异具有统计学意义(P0.05);且治疗后治疗组的肿瘤标志物水平均显著低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,治疗组的CD3~+、CD4~+和CD4~+/CD8~+水平均显著升高,CD8~+水平显著降低,同组治疗前后比较差异具有统计学意义(P0.05);且治疗后治疗组免疫因子水平显著优于对照组,两组比较差异具有统计学意义(P0.05)。结论复方苦参注射液联合ET方案治疗晚期乳腺癌疗效确切,能降低肿瘤标志物水平,提高免疫功能,延长患者PFS和OS,提高患者生活质量,具有一定的临床推广应用价值。     

Late-phase investigational approaches for the treatment of relapsed/refractory acute myeloid leukemia

Introduction: Acute myeloid leukemia (AML) is a malignant hematologic disorder that affects more than 13,000 adults each year in the USA. Despite continued advances in the understanding of the molecular pathogenesis of the disease and patient management, the cure rate for AML remains relatively low, largely due to a high rate of relapsed or refractory disease.

Areas covered: The purpose of this review is to provide an understanding of the unmet needs in relapsed/refractory AML, and to assess promising investigational agents with ongoing or planned Phase III clinical trials.

Expert opinion: Although the treatment of relapsed/refractory AML remains a challenge, numerous new chemotherapeutics are currently in development. Enrollment in clinical trials should be strongly considered for patients with relapsed/refractory disease, and emerging data may help identify new agents with significant activity in this setting.     

An indirect comparison of the efficacy of bevacizumab plus carboplatin and paclitaxel versus pemetrexed with cisplatin in patients with advanced or recurrent non-squamous adenocarcinoma non-small cell lung cancer

Abstract

Objective:

There are two new treatment options available for the treatment of adenocarcinoma histology non-small cell lung cancer (NSCLC) which offer improved benefit in terms of progression-free (PFS) and overall survival (OS) over chemotherapy. Both bevacizumab and pemetrexed when combined with chemotherapy significantly increase PFS and OS in patients with advanced NSCLC versus chemotherapy alone. The aim of this analysis was to compare the efficacy for patients with non-squamous adenocarcinoma NSCLC treated with bevacizumab, carboplatin and paclitaxel (BCP) to pemetrexed and cisplatin (PC) by using indirect comparison (ITC) methodology.