Quinacrine Enhances Cisplatin-Induced Cytotoxicity in Four Cancer Cell Lines

Background: Toll-like receptor 3 (TLR3) activation in tumor cells induces apoptosis. We investigated the effect of TLR3 ligand (poly(I:C)) in combination with chemotherapeutics applied to human pharyngeal carcinoma cells as a possible antitumor therapy. Methods:Human pharyngeal cancer cell lines were studied (FaDu and Detroit 562). Cytotoxicity assays and apoptosis assays (annexin V staining and caspase 3/7 activity measurements) were used to investigate the cytotoxic effects. By using TLR3 siRNA we confirmed that the observed effect is TLR3-dependent. Results: We found that the combined application of poly(I:C) and chemotherapeutics (cisPt, HU, 5-FU and MTX) has a stronger inhibitory effect on cell growth in tumor cells expressing functional TLR3 as compared with a single treatment. This is a result of TLR3-dependent apoptosis. Conclusion: Our study showed that a combined application of the two agents already being used in tumor therapy could lower the necessary dosage of chemotherapeutics, leading to fewer side effects.

Section: Discussionmentioning

confidence: 99%

Antitumor Activity from the Combined Application of Poly(I:C) and Chemotherapeutics in Human Metastatic Pharyngeal Cell Lines

Matijević¹,

Kirinec²,

Pavelić³

2011

“…In vitro studies have demonstrated the effect of taxanes and cisplatin in head and neck cell lines and further support the biological rationale for adopting a regimen that contains the two drugs [26]. …”

Section: Discussionmentioning

confidence: 99%

Addition of Taxane to Induction Therapy in Head and Neck Malignancies: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Perl¹,

Ben‐Aharon²,

Popovtzer³

et al. 2013

Background: Head and neck cancer, mostly squamous cell carcinoma, ranks sixth among the most common cancers. Despite progress in treatment in recent years, survival remains poor. Since induction chemotherapy has been associated with survival benefit, it is a reasonable treatment option. The standard protocol up to recently has been cisplatin and 5-flourouracil. The addition of taxanes to the standard induction protocol has shown superiority in terms of the overall response rate. Nevertheless, not all trials demonstrated survival benefit. We aimed to evaluate the effect of taxane added to the standard protocol of induction therapy. Methods: We performed a systematic review and meta-analysis of randomized controlled trials that compared the addition of taxane to the standard induction protocol of cisplatin and 5-flourouracil for patients with head and neck malignancy. We searched The Cochrane library, PubMed, LILACS, conference proceedings, and references of published trials. Two reviewers independently assessed the quality of the trials and extracted data. Hazard ratios (HRs) for time-to-event were determined and pooled. Results: A total of 4 trials comprising 1,441 patients were included in this meta-analysis. All patients were available for the meta-analysis of overall survival. Patients treated with the addition of taxane had statistically significant overall survival [HR = 0.82, 95% confidence interval (CI) 0.71-0.94] and progression-free survival (HR = 0.82, 95% CI 0.72-0.93). No effect was observed in larynx preservation rate (relative risk = 0.88, 95% CI 0.64-1.19). The rate of hematological adverse events was higher in the taxane group than in the control group. Conclusions: These results suggest that induction therapy with the addition of taxane is superior to induction therapy with cisplatin and 5-flourouracil in terms of overall survival and progression-free survival. The higher rate of neutropenia and neutropenic fever should be taken into consideration when making treatment decisions.

“…In conclusion, our findings suggest that the MI combination is not recommended for clinical use in patients with gemcitabine-resistant pancreatic cancer. We need to know more for a better selection of patients [7,31,44] and to gain additional information on the biological and molecular characteristics of this disease [45,46] to be able to individuate new and more effective agents [47,48]. At the present time, in the absence of a standard salvage therapy, the best therapeutic option for patients with gemcitabine-resistant pancreatic cancer should be the enrollment in a phase I–II clinical trial.…”

Section: Discussionmentioning

confidence: 99%

Salvage Therapy with Mitomycin and Ifosfamide in Patients with Gemcitabine-Resistant Metastatic Pancreatic Cancer: A Phase II Trial

Cereda¹,

Reni²,

Rognone³

et al. 2011

Background: At the time of upfront treatment failure, over half of the patients with advanced pancreatic cancer are candidates for further treatment. Methods: Patients with metastatic gemcitabine-resistant pancreatic cancer were treated with mitomycin 8 mg/m² on day 1, ifosfamide 2,500 mg/m² and mesna 3,000 mg/m² on days 1–3 every 28 days until progressive disease. A positive responder was defined as a patient who was progression free at 6 months from trial enrolment. According to the Fleming design, a sample size of 34 patients was estimated assuming p0 = 0.05 and p1 = 0.20. Results: Between May 2006 and December 2007, 21 patients (median age 56 years; median Karnofsky performance score 80) were enrolled. One patient died before receiving any treatment. Eighteen patients interrupted chemotherapy due to progressive disease (n = 15), toxicity (n = 2) or refusal (n = 1). Grade >2 toxicity consisted of neutropenia in 80% of patients, thrombocytopenia and fatigue in 20% and anemia in 10%. Only 1 patient was progression free at 6 months (5%). One patient had a partial response (5%) and 2 patients had stable disease (10%). Median survival was 3.7 months. Conclusion: Based on the poor outcome observed and on the high level of grade 3–4 toxicity, the trial was prematurely stopped and the mitomycin and ifosfamide regimen was considered insufficiently active in gemcitabine-pretreated advanced pancreatic cancer.