Pre-operative chemoradiotherapy using capecitabine and cetuximab followed by definitive surgery in patients with operable rectal cancer

Bazarbashi, Shouki; Omar, Ayman; Aljubran, Ali; Alzahrani, Ahmad; Al‐Sanea, Nasser; Abduljabbar, Alaa; Alhomoud, Samar; Ashari, Luai H.; Balaraj, Khalid; Soudy, Hussein; Neimatallah, Mohammad; Fagih, Musa

doi:10.1016/j.hemonc.2016.08.004

Cited by 6 publications

(10 citation statements)

References 35 publications

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“…[44][45][46][47] Even in recent trials focused on wild-type KRAS rectal cancer, the response to neoadjuvant treatment was not markedly improved over response rates to 5FU/RT alone. 48,49 Thus, we also evaluated our unique patient-derived in vitro and in vivo models as experimental therapy testing platforms in order to develop future precision medicine strategies. Using our in vitro platform, we observed an increased response to cetuximab in two of four PDTOs with wild-type KRAS similar to the clinical observation that 50% of mCRC patients with wild-type KRAS do not benefit from anti-EGFR therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Cetuximab has shown promise in CRC cell line in vitro and in vivo models when combined with RT, although the combination of cetuximab with 5FU/RT in rectal cancer has failed to improve clinical response . Even in recent trials focused on wild‐type KRAS rectal cancer, the response to neoadjuvant treatment was not markedly improved over response rates to 5FU/RT alone . Thus, we also evaluated our unique patient‐derived in vitro and in vivo models as experimental therapy testing platforms in order to develop future precision medicine strategies.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Modeling rectal cancer to advance neoadjuvant precision therapy

Janakiraman

Zhu

Becker

et al. 2020

Intl Journal of Cancer

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Progress in rectal cancer therapy has been hindered by the lack of effective disease-specific preclinical models that account for the unique molecular profile and biology of rectal cancer. Thus, we developed complementary patient-derived xenograft (PDX) and subsequent in vitro tumor organoid (PDTO) platforms established from preneoadjuvant therapy rectal cancer specimens to advance personalized care for rectal cancer patients. Multiple endoscopic samples were obtained from 26 Stages 2 and 3 rectal cancer patients prior to receiving 5FU/RT and implanted subcutaneously into NSG mice to generate 15 subcutaneous PDXs. Second passaged xenografts demonstrated 100% correlation with the corresponding human cancer histology with maintained mutational profiles. Individual rectal cancer PDXs reproduced the 5FU/RT response observed in the corresponding human cancers. Similarly, rectal cancer PDTOs reproduced significant heterogeneity in cellular morphology and architecture. PDTO in vitro 5FU/RT treatment response replicated the clinical 5FU/RT neoadjuvant therapy pathologic response observed in the corresponding patient tumors (p < 0.05). The addition of cetuximab to the 5FU/RT regiment was significantly more sensitive in the rectal cancer PDX and PDTOs with wild-type KRAS compared to mutated KRAS (p < 0.05). Considering the close relationship between the patient's cancer and the corresponding PDX/PDTO, rectal cancer patient-derived research platforms represent powerful translational research resources as population-based tools for biomarker discovery and experimental therapy testing. In addition, our findings suggest that cetuximab may enhance RT effectiveness by improved patient selection based on mutational profile in addition to KRAS or by developing a protocol using PDTOs to identify sensitive patients. H.J. and Y.Z. contributed equally to this work Additional Supporting Information may be found in the online version of this article.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Modeling rectal cancer to advance neoadjuvant precision therapy

Janakiraman

Zhu

Becker

et al. 2020

Intl Journal of Cancer

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“…Recently, the combination of new therapies, such as molecular-targeted therapies, with RT has demonstrated improved outcomes for CRC [52]. These new drugs may not only enhance the antitumor effect of radiation but also increase damage to normal tissues.…”

Section: Future Prospects Of Cirtmentioning

confidence: 99%

Carbon-ion Radiotherapy for Colorectal Cancer

Yamada

Takiyama

Isozaki

et al. 2021

J Anus Rectum Colon

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“…Yang et al [13] investigated the efficacy and safety of a combined preoperative regimen, including volumetric modulated arc 24.1% (G3: 0% vs. 1.3%; p = 0.04) pCR, pathological complete response; DFS, disease-free survival; OS, overall survival; 3DCRT, three-dimensional conformal radiotherapy; ND, not defined; IMRT, intensity-modulated radiation therapy; GI, gastrointestinal; GU, genitourinary; CRT, chemoradiotherapy; CAPOX, capecitabine and oxaliplatin; VMAT, volumetric modulated arc therapy; NS, not significant; G, grade. therapy (VMAT) along with a simultaneous integrated boost consisting of 58.75 Gy (2.35 Gy per fraction) to mesorectum and 50 Gy (2 Gy per fraction) for other pelvic lymph node stations, with concurrent capecitabine.…”

Section: Radiotherapy Intensificationmentioning

confidence: 99%

“…Bazarbashi et al [ 24 ] studied the effect of adding weekly cetuximab to capecitabine concurrent with RT. The authors concluded that this combination was attainable with acceptable toxicity in LARC, and it was associated with better pCR compared to historical controls.…”

Section: Concurrent Chemotherapy Intensificationmentioning

confidence: 99%

Current approaches in intensification of long-course chemoradiotherapy in locally advanced rectal cancer: a review

et al. 2021

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Rectal cancer is one of the most prevalent cancers in the world. In many countries, the current standard of care is long-course chemoradiation (CRT), followed by total mesorectal excision. Some efforts have been made by intensifying radiation or chemotherapy components of the neoadjuvant therapy to further decrease the local recurrence and augment surgery's feasibility and improve the oncological outcomes. This paper reviews recent intensified neoadjuvant interventions in locally advanced rectal cancer (LARC) in terms of efficacy and treatment-related toxicity. Many maneuvers have been made so far to improve the oncological outcomes of rectal cancer with intensified neoadjuvant longcourse CRT. Some of these approaches seem compelling and deserve further study, while some have just increased the treatment-related toxicities without evident benefits. Those endeavors with greater pathological complete response than the standard of care may make us await the long-term results on survival rates and chronic treatment-related toxicity. After introduction of neoadjuvant CRT for LARC there have been many efforts to improve its outcomes. Here, this study gathered most of these efforts that intensified the neoadjuvant therapy with some being promising and some being futile.

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Pre-operative chemoradiotherapy using capecitabine and cetuximab followed by definitive surgery in patients with operable rectal cancer

Abstract: Adding cetuximab to pre-operative concurrent capecitabine and radiotherapy provides modest efficacy with manageable toxicity.

Cited by 6 publications

References 35 publications

Modeling rectal cancer to advance neoadjuvant precision therapy

Modeling rectal cancer to advance neoadjuvant precision therapy

Carbon-ion Radiotherapy for Colorectal Cancer

Current approaches in intensification of long-course chemoradiotherapy in locally advanced rectal cancer: a review

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