Cancers, Vol. 9, Pages 146: Advances in Precision Medicine: Tailoring Individualized Therapies

Cancers, Vol. 9, Pages 146: Advances in Precision Medicine: Tailoring Individualized Therapies

Cancers doi: 10.3390/cancers9110146

Authors: Kyle Matchett Niamh Lynam-Lennon R. Watson James Brown

The traditional bench-to-bedside pipeline involves using model systems and patient samples to provide insights into pathways deregulated in cancer. This discovery reveals new biomarkers and therapeutic targets, ultimately stratifying patients and informing cohort-based treatment options. Precision medicine (molecular profiling of individual tumors combined with established clinical-pathological parameters) reveals, in real-time, individual patient's diagnostic and prognostic risk profile, informing tailored and tumor-specific treatment plans. Here we discuss advances in precision medicine presented at the Irish Association for Cancer Research Annual Meeting, highlighting examples where personalized medicine approaches have led to precision discovery in individual tumors, informing customized treatment programs.

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Phase II study of fixed dose-rate gemcitabine plus S-1 as a second-line treatment for advanced biliary tract cancer

Abstract

Purpose

Gemcitabine plus platinum is considered standard first-line chemotherapy for patients with advanced biliary tract cancer. However, no standard second-line therapy has been established for this disease. According to reports, S-1 exerts anti-tumor effects on advanced biliary tract cancer and gemcitabine is more effective via fixed dose-rate administration. We evaluated the efficacy and safety of a combination of fixed dose-rate gemcitabine and S-1 after failure of gemcitabine or gemcitabine plus cisplatin therapy.

Methods

This single-arm phase II study (clinical trial number: UMIN000005918) set the response rate as the primary endpoint and used a MiniMax two-stage design with a null hypothesis < 7% and alternative hypothesis ≥ 25%. Thirty-five patients were needed to yield a power of 90% and α value of 0.05. Patients received gemcitabine (1000 mg/m², div, 100-min period, day 1) and S-1 (40 mg/m² twice daily, oral, days 1–7), every 2 weeks until disease progression or intolerable adverse events were observed.

Results

Forty-one patients were enrolled, and 3 of 23 first-stage patients responded. The overall response rate was 9.8% [95% confidence interval (CI): 2.7–19.2%]. The median overall and progression-free survival were 7.0 [95% CI: 5.3–8.6] and 2.6 months (95% CI: 1.6–3.5), respectively. The most common grade 3–4 adverse events were leukopenia (19.5%), neutropenia (19.5%), anemia (14.6%), thrombocytopenia (7.3%), and anorexia (4.8%).

Conclusion

Second-line fixed dose-rate gemcitabine plus S-1 was not sufficiently effective and tolerable in patients with advanced biliary tract cancer refractory to gemcitabine or gemcitabine plus cisplatin.

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Cancers, Vol. 9, Pages 146: Advances in Precision Medicine: Tailoring Individualized Therapies

Cancers, Vol. 9, Pages 146: Advances in Precision Medicine: Tailoring Individualized Therapies

Cancers doi: 10.3390/cancers9110146

Authors: Kyle Matchett Niamh Lynam-Lennon R. Watson James Brown

The traditional bench-to-bedside pipeline involves using model systems and patient samples to provide insights into pathways deregulated in cancer. This discovery reveals new biomarkers and therapeutic targets, ultimately stratifying patients and informing cohort-based treatment options. Precision medicine (molecular profiling of individual tumors combined with established clinical-pathological parameters) reveals, in real-time, individual patient's diagnostic and prognostic risk profile, informing tailored and tumor-specific treatment plans. Here we discuss advances in precision medicine presented at the Irish Association for Cancer Research Annual Meeting, highlighting examples where personalized medicine approaches have led to precision discovery in individual tumors, informing customized treatment programs.

http://ift.tt/2yMsBS4

Current and emerging treatment strategies for children with progressive chiasmatic-hypothalamic glioma diagnosed as infants: a web-based survey

Abstract

Treatment of infant hypothalamic chiasmatic glioma (iCHG) is challenging, about 30% of the children progress during chemotherapy. Despite subsequent treatments the 5 year overall-survival rate is only 70%. This study investigates treatment strategies currently applied for progressive iCHG. A web-based questionnaire was sent out to the members of the SIOPE Brain Tumour Group asking for current second and third line strategies at progression during and after the end of first line therapy. The questionnaire was answered by 47 paediatric oncologists from 15 countries. iCHG progressing during first line therapy with carboplatin-vincristine would be considered for treatment with alternative chemotherapy by 17 (36%) and with surgery plus chemotherapy by 27 respondents (58%). Components suggested for second line were vinblastine (62%), cisplatin (34%) and cyclophosphamide (26%). For third line therapy bevacizumab (BVZ) was considered as suitable by respondents in 53% (often with irinotecan 40%) and vinblastine by 34% respectively. Experience with BVZ in CHG is shown by 53% of respondents regarding at least 95 patients (median treated 1–5 patients per respondent at any age) with a median BVZ administration over 12 months. Effectiveness was reported varying between stable disease and regression while complications were rarely stated (proteinuria, hypertension, bleeding). BVZ would be available to 85% of respondents as therapeutic option for iCHG patients. Multiple anti-neoplastic drug regimens are applied for progressive iCHG, partly considered in combination with surgery if safely feasible. BVZ is commonly used at a satisfactory level in third line, mainly combined with irinotecan.

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Phase II study of fixed dose-rate gemcitabine plus S-1 as a second-line treatment for advanced biliary tract cancer

Abstract

Purpose

Gemcitabine plus platinum is considered standard first-line chemotherapy for patients with advanced biliary tract cancer. However, no standard second-line therapy has been established for this disease. According to reports, S-1 exerts anti-tumor effects on advanced biliary tract cancer and gemcitabine is more effective via fixed dose-rate administration. We evaluated the efficacy and safety of a combination of fixed dose-rate gemcitabine and S-1 after failure of gemcitabine or gemcitabine plus cisplatin therapy.

Methods

This single-arm phase II study (clinical trial number: UMIN000005918) set the response rate as the primary endpoint and used a MiniMax two-stage design with a null hypothesis < 7% and alternative hypothesis ≥ 25%. Thirty-five patients were needed to yield a power of 90% and α value of 0.05. Patients received gemcitabine (1000 mg/m², div, 100-min period, day 1) and S-1 (40 mg/m² twice daily, oral, days 1–7), every 2 weeks until disease progression or intolerable adverse events were observed.

Results

Forty-one patients were enrolled, and 3 of 23 first-stage patients responded. The overall response rate was 9.8% [95% confidence interval (CI): 2.7–19.2%]. The median overall and progression-free survival were 7.0 [95% CI: 5.3–8.6] and 2.6 months (95% CI: 1.6–3.5), respectively. The most common grade 3–4 adverse events were leukopenia (19.5%), neutropenia (19.5%), anemia (14.6%), thrombocytopenia (7.3%), and anorexia (4.8%).

Conclusion

Second-line fixed dose-rate gemcitabine plus S-1 was not sufficiently effective and tolerable in patients with advanced biliary tract cancer refractory to gemcitabine or gemcitabine plus cisplatin.

http://ift.tt/2zCNsVJ

Phenotypic and genotypic heterogeneity of Lynch syndrome: a complex diagnostic challenge

Abstract

Lynch syndrome is the hereditary disorder that most frequently predisposes to colorectal cancer as well as predisposing to a number of extracolonic cancers, most prominently endometrial cancer. It is caused by germline mutations in the mismatch repair genes. Both its phenotype and genotype show marked heterogeneity. This review gives a historical overview of the syndrome, its heterogeneity, its genomic landscape, and its implications for complex diagnosis, genetic counseling and putative implications for immunotherapy.

http://ift.tt/2zCI1pH

Severe liver toxicity in a chronic myeloid leukemia patient probably induced by a drug interaction between imatinib and sertraline

Journal of Oncology Pharmacy Practice, Ahead of Print.


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