Meta-analysis of regression of advanced solid tumors in patients receiving placebo or no anti-cancer therapy in prospective trials

We performed a systematic review and meta-analysis to evaluate the role of gastric acid suppressant use on outcomes of tyrosine kinase inhibitors (TKIs) and oral chemotherapy. We identified all research evaluating the effect of GAS (gastric acid suppressants) use on patients receiving oral chemotherapy or TKIs for solid tumors. The pooled hazard ratios (HRs) and 95% confidence interval (95%CI) for overall survival (OS) and progression-free survival (PFS) were calculated with a fixed-effects or a random effects model. The study population included n = 16 retrospective studies and 372,418 patients. The series concerned gastrointestinal tract tumors (n = 5 studies), renal cell carcinomas (RCC, n = 3 studies), non-small cell lung cancers (NSCLC, n = 5 studies), and soft tissue sarcomas or mixed histologies solid tumors in n = 3 studies. The pooled HRs for OS and PFS were 1.31 (95%CI: 1.20–1.43; p < 0.01) and 1.3 (95%CI 1.07–1.57; p < 0.01) for GAS and no GAS users, respectively. Only studies of EGFR (epidermal growth factor receptor) mutated NSCLC patients receiving TKIs and those with colorectal cancer receiving oral chemotherapy showed a significant correlation between GAS and poor survival. Our study supports the evidence of a possible negative impact of concomitant GAS therapy on survival outcomes of patients receiving oral anti-cancer drugs.

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Adverse events risk associated with regorafenib in the treatment of advanced solid tumors: meta-analysis of randomized controlled trials

OncoTargets and Therapy ◽

10.2147/ott.s156760 ◽

2018 ◽

Vol Volume 11 ◽

pp. 6405-6414 ◽

Cited By ~ 11

Author(s):

Xiaonan Yin ◽

Yuan Yin ◽

Chaoyong Shen ◽

Huijiao Chen ◽

Jiang Wang ◽

...

Keyword(s):

Adverse Events ◽

Randomized Controlled Trials ◽

Solid Tumors ◽

Meta Analysis ◽

Controlled Trials ◽

Advanced Solid Tumors ◽

Randomized Controlled

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Integrating the drug, disulfiram into the vitamin E-TPGS-modified PEGylated nanostructured lipid carriers to synergize its repurposing for anti-cancer therapy of solid tumors

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2018.12.051 ◽

2019 ◽

Vol 557 ◽

pp. 374-389 ◽

Cited By ~ 16

Author(s):

Parikshit Banerjee ◽

Tianjiao Geng ◽

Arpan Mahanty ◽

Tiantian Li ◽

Li Zong ◽

...

Keyword(s):

Vitamin E ◽

Cancer Therapy ◽

Solid Tumors ◽

Nanostructured Lipid Carriers ◽

Vitamin E Tpgs ◽

Anti Cancer

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Risk of venous thromboembolism in cancer patients treated with cisplatin: A systematic review and meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e21016 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e21016-e21016

Author(s):

Sonia Maria Seng ◽

Ziyue Liu ◽

Sophia Chiu ◽

Tracey Proverbs-Singh ◽

Guru Sonpavde ◽

...

Keyword(s):

Relative Risk ◽

Solid Tumors ◽

Meta Analysis ◽

Systemic Review ◽

Advanced Solid Tumors ◽

Thromboembolic Events ◽

Patients With Cancer ◽

Increased Risk ◽

Venous Thromboembolic Events ◽

Venous Thromboembolic

e21016 Background: Several reports suggest that cisplatin is associated with an increased risk of thromboembolism (TE). However, patients with solid tumors have multiple risk factors for TE and the excess risk of venous thromboembolic events (VTEs) with cisplatin-based chemotherapy as compared with non-cisplatin-based chemotherapy has not been well described. We performed a systemic review and meta-analysis of randomized controlled trials (RCTs) evaluating the incidence and risk of VTE associated with cisplatin-based chemotherapy. Methods: PubMed was searched for articles published from January 1, 1990 until December 31, 2010.The primary aim was to evaluate the association between treatment with cisplatin and VTEs in patients with cancer. Clinical trials that met the following criteria were included in the meta-analysis: (1) prospective randomized phase 2 and 3 trials of patients with cancer; (2) randomization to treatment with cisplatin versus a non-cisplatin containing chemotherapy regimen (3) available data on venous thromboembolic events. Data on all grade venous thromboembolic events was extracted. Study quality was calculated utilizing Jadad scores. Incidence rates, relative risks, and 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup analyses included the impact of publication year, tumor type, and cisplatin dose. Results: A total of 8216 patients with a variety of advanced solid tumors from 38 RCTs were included for analysis. Among patients treated with cisplatin-based chemotherapy, the summary incidence of VTE was 1.64% (95% CI, 1.06–2.25). Patients treated with cisplatin-based chemotherapy had a significantly increased risk of VTE with a relative risk of 1.65 (95% CI, 1.25–2.18; P = .01) compared with controls. Exploratory subgroup analysis revealed the highest relative risk of VTE in patients receiving a weekly equivalent cisplatin dose >30 mg/m2 (2.64; 95% CI, 1.18–5.77; P = .02) and in studies reported during 2000-2010 (1.70; 95% CI, 1.27–2.28; P = .01). Conclusions: Cisplatin chemotherapy is associated with a significant increase in the risk of VTE in patients with advanced solid tumors compared with non-cisplatin chemotherapy.

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Phase I trial of trebananib (AMG 386) plus temsirolimus (Tr + T) in patients (pts) with advanced solid tumors (PJC-008/NCI#9041).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.2534 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 2534-2534

Author(s):

David Shao Peng Tan ◽

Christian K. Kollmannsberger ◽

Sebastien J. Hotte ◽

David W. Cescon ◽

Ivan Diaz-Padilla ◽

...

Keyword(s):

Flow Cytometry ◽

Antitumor Activity ◽

Solid Tumors ◽

Tumor Response ◽

Maximum Tolerated Dose ◽

Advanced Solid Tumors ◽

Treatment Benefit ◽

Amg 386 ◽

Anti Cancer ◽

Limb Edema

2534 Background: Preclinical data suggest that combined Ang1/2 and mTOR blockade has synergistic anti-cancer activity. The combination of Tr (inhibits angiogenesis by preventing interaction of Ang1/2 with Tie2) with the mTOR inhibitor T was evaluated in pts with advanced solid tumors to determine safety, tolerability, maximum tolerated dose (MTD), pharmacodynamics and preliminary antitumor activity. Methods: Pts were enrolled using 3+3 design. Tr and T were dosed on Day 1 (D1), 8, 15 and 22 of a 28-day cycle. Peripheral blood was collected for evaluation of Tie2-expressing monocytes (TEMs) and thymidine phosphorylase (TP) (an angiogenic enzyme increased in TEMs upon Tie2 stimulation) by flow cytometry. Tumor response was assessed every 2 cycles. Results: 13 pts have been enrolled, 6 at dose level (DL) 1 (15mg/kg Tr + 25mg T) and 7 (1 died from disease before DLT assessment) at DL -1 (15mg/kg Tr + 20mg T). Median age was 57yrs, ECOG 0-1, median previous chemotherapy lines 3 (range 1-8). In DL 1, 1/6 pts experienced DLT (Grade (Gr) 2 pneumonitis). In view of frequent Gr2 adverse events (AEs) in DL 1, DL -1 was evaluated with DLTs in 2/6 evaluable pts (Gr3 mucositis and intolerable Gr2 limb edema preventing start of cycle 2 within 14 days). The most common related AEs (all Gr across both DL) were: fatigue (77%), edema (69%), anorexia (62%), and nausea (54%). Common Gr≥3 AEs included lymphopenia (23%) and fatigue (23%). Of 10 evaluable pts, best RECIST responses were: 1 breast cancer pt (ER+/ HER2-/ PIK3CA mutant) with PR (now in cycle 9), 7 pts with SD, and 2 pts with PD. Four pts with ovarian cancer (1 PIK3CAmutant) had SD ≥11weeks with 2/3 pts (1 not evaluable) demonstrating GCIG response (>50% decrease in CA125). In preliminary analyses, TP expression in TEMs was decreased (mean -18%) in 4pts with tumor shrinkage, but increased (+6%) in 1pt with tumor growth, suggesting a trend between reduced TP and tumor response. Conclusions: The MTD was exceeded at 15mg/kg Tr and 20mg T weekly. The safety of 10mg/kg Tr and 20mg T weekly is currently being evaluated. The combination of Tr and T shows early signs of antitumor activity. TP expression in TEMs by flow cytometry as an early marker of treatment benefit warrants further evaluation. Clinical trial information: NCT01548482.

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