A Prospective Pilot Study of Target-guided Personalized Chemotherapy with Intensity-modulated Radiotherapy in Patients With Early Rectal Cancer

Cubillo, Antonio; Hernando-Requejo, Ovidio; García-García, Elena; Rodríguez-Pascual, Jesús; Vicente, Emilio; Morelli, P.; Rubio, Carmen; López‐Ríos, Fernando; Muro, Avertano; López, Ulpiano; Prados, Susana; Quijano, Yolanda; Hidalgo, Manuel

doi:10.1097/coc.0b013e31826e0703

Cited by 21 publications

(13 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Studies on gastrointestinal cancers have suggested that overexpression of TOP1 predicts benefit of camptothecin-based therapies [84–88]. However, the evidence associated with the predictive effect of TOP1 expression status and therapy outcome was mostly of low-level and studies often reported inconclusive results [89–91] (Figure 2).…”

Section: Resultsmentioning

confidence: 99%

Quantification and expert evaluation of evidence for chemopredictive biomarkers to personalize cancer treatment

et al. 2016

View full text Add to dashboard Cite

Predictive biomarkers have the potential to facilitate cancer precision medicine by guiding the optimal choice of therapies for patients. However, clinicians are faced with an enormous volume of often-contradictory evidence regarding the therapeutic context of chemopredictive biomarkers.We extensively surveyed public literature to systematically review the predictive effect of 7 biomarkers claimed to predict response to various chemotherapy drugs: ERCC1-platinums, RRM1-gemcitabine, TYMS-5-fluorouracil/Capecitabine, TUBB3-taxanes, MGMT-temozolomide, TOP1-irinotecan/topotecan, and TOP2A-anthracyclines. We focused on studies that investigated changes in gene or protein expression as predictors of drug sensitivity or resistance. We considered an evidence framework that ranked studies from high level I evidence for randomized controlled trials to low level IV evidence for pre-clinical studies and patient case studies.We found that further in-depth analysis will be required to explore methodological issues, inconsistencies between studies, and tumor specific effects present even within high evidence level studies. Some of these nuances will lend themselves to automation, others will require manual curation. However, the comprehensive cataloging and analysis of dispersed public data utilizing an evidence framework provides a high level perspective on clinical actionability of these protein biomarkers. This framework and perspective will ultimately facilitate clinical trial design as well as therapeutic decision-making for individual patients.

show abstract

Section: Resultsmentioning

confidence: 99%

Quantification and expert evaluation of evidence for chemopredictive biomarkers to personalize cancer treatment

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Nevertheless, a pilot study of RT with personalized chemotherapy and biological therapy based on molecular markers (TOPO-1, ERCC1 expression, KRAS, BRAF, and PI3K) used capecitabine and either irinotecan (if TOPO-1 high) or oxaliplatin (if ERCC1 low), and either VEGF-or EGFR-targeted agents (if KRAS wildtype) among 16 patients with T3 or N1 rectal cancers [68]. The ypCR rate was promising at 50 %, which offers a potential basis for future molecularly driven larger studies.…”

Section: Anti-epidermal Growth Factor Therapymentioning

confidence: 99%

Is There a Best Radiosensitizing Agent in the Treatment of Locally Advanced Rectal Cancer?

Coveler

Richard

Apisarnthanarax

et al. 2016

Curr Colorectal Cancer Rep

View full text Add to dashboard Cite

Over the past several decades, the management of localized rectal cancer has evolved from surgery alone as the definitive treatment to incorporating both radiation and chemotherapy to improve rates of local control and disease-free survival. Several chemoradiation regimens have been tested with different mechanisms of action, efficacy, and toxicity. There is little debate that concurrent radiation and a fluoropyrimidine (5-fluorouracil (5-FU) or capecitabine) is the current standard of care prior to total mesorectal excision (TME). Attempts to add additional chemotherapy, such as oxaliplatin or irinotecan, have not consistently improved results. Recent attention has been given to concurrent biologic therapies (vascular endothelial growth factor (VEGF)-, epidermal growth factor receptor (EGFR)-, Poly(ADP-ribose) polymerase (PARP)-inhibitors, etc.) which may improve the outcomes of multi-modality therapy; however, the evidence is limited to phase I/II trials. It is critical for oncologists to be aware of various radiosensitizing agents that have been investigated and which will provide the best chance of disease control. In this review, we describe the mechanisms of action and evidence supporting these regimens to determine if there is a best radiosensitizing agent. Furthermore, we describe the relevant studies investigating the recent use of biologic radiosensitizers and the future direction using those agents.

show abstract

“…There is currently no role for the addition of EGFR‐targeted therapy as a radiosensitizer in the treatment of LARC. However, a pilot study of RT with personalized chemotherapy and biological therapy, based on molecular markers among 16 patients with T3 or N1 rectal cancers, showed a pCR rate of 50 per cent, which may be the basis for future molecular guided studies.…”

Section: Epidermal Growth Factor Receptor Inhibitorsmentioning

confidence: 99%

Systematic review of treatment intensification using novel agents for chemoradiotherapy in rectal cancer

Clifford

Govindarajah

Parsons

et al. 2018

British Journal of Surgery

View full text Add to dashboard Cite

BackgroundWith the well established shift to neoadjuvant treatment for locally advanced rectal cancer, there is increasing focus on the use of radiosensitizers to improve the efficacy and tolerability of radiotherapy. There currently exist few randomized data exploring novel radiosensitizers to improve response and it is unclear what the clinical endpoints of such trials should be.MethodsA qualitative systematic review was performed according to the PRISMA guidelines using preset search criteria across the PubMed, Cochrane and Scopus databases from 1990 to 2017. Additional results were generated from the reference lists of included papers.ResultsA total of 123 papers were identified, of which 37 were included; a further 60 articles were obtained from additional referencing to give a total of 97 articles. Neoadjuvant radiosensitization for locally advanced rectal cancer using fluoropyrimidine‐based chemotherapy remains the standard of treatment. The oral derivative capecitabine has practical advantages over 5‐fluorouracil, with equal efficacy, but the addition of a second chemotherapeutic agent has yet to show a consistent significant efficacy benefit in randomized clinical assessment. Preclinical and early‐phase trials are progressing with promising novel agents, such as small molecular inhibitors and nanoparticles.ConclusionDespite extensive research and promising preclinical studies, a definite further agent in addition to fluoropyrimidines that consistently improves response rate has yet to be found.

show abstract

A Prospective Pilot Study of Target-guided Personalized Chemotherapy with Intensity-modulated Radiotherapy in Patients With Early Rectal Cancer

Abstract: The individualization of neoadjuvant chemotherapy in patients with rectal cancer is feasible and leads to a high rate of pathologic response.

Cited by 21 publications

References 29 publications

Quantification and expert evaluation of evidence for chemopredictive biomarkers to personalize cancer treatment

Quantification and expert evaluation of evidence for chemopredictive biomarkers to personalize cancer treatment

Is There a Best Radiosensitizing Agent in the Treatment of Locally Advanced Rectal Cancer?

Systematic review of treatment intensification using novel agents for chemoradiotherapy in rectal cancer

Contact Info

Product

Resources

About