Penile metastasis in rectal cancer with pathologic complete response after neoadjuvant chemoradiotherapy

e15144 Background: There is strong interest in the development of novel agents to further improve the therapeutic ratio of neoadjuvant chemoradiotherapy for rectal cancer. CRLX101 is an investigational nanoparticle-drug conjugate with a camptothecin payload. The purpose of this Phase Ib/II study is to assess toxicity and to evaluate whether the addition of CRLX101 to chemoradiotherapy can improve pathologic complete response (pCR) for rectal cancer. Methods: This is a single-arm multicenter Phase Ib/II study examining the addition of CRLX101 to a standard capecitabine-based chemoradiotherapy regimen. Phase Ib employs a 3+3 dose escalation design with starting dose of 12 mg/m2 every other week (QOW). Dose level +1 was 15 mg/m2 (MTD for CRLX101 single agent QOW). Upon reaching MTD for QOW dosing, protocol was modified to evaluate QW CRLX101 dosing starting at 12 mg/m2 and 15 mg/m2as +1 level. Secondary endpoints included pCR and clinical outcome. Results: A total of 32 patients were enrolled on the trial. 26/32 had T3-4, 9/32 had N2 and 16/32 had N1 disease. For QOW dosing, 9 patients completed treatment without DLT and MTD was identified as 15 mg/m2 QOW. 14 patients were treated on the Phase II portion of the study at 15 mg/m2 QOW prior to the initiation of weekly dosing Phase Ib cohorts. For QW dosing, 0/3 patients experienced DLT at 12 mg/m2 and 1/6 patients experienced DLT at 15 mg/m2. The DLT was skin desquamation requiring treatment delay. QW MTD was identified as 15 mg/m2. Toxicities (all grade 3 except lymphopenia) that could possibly be attributed to CRLX101 are in Table 1. Full clinical and pathologic staging were available for 29/32 patients. Mean neoadjuvant rectal (NAR) score was 19 with standard deviation of 15. At the weekly MTD, 3/6 patients had pCR. Conclusions: CRLX101 weekly at 15 mg/m2+ standard capecitabine-based chemoradiotherapy appears to be well tolerated, with promising pCR rates that warrants further evaluation. A larger PhII trial should be considered with this regimen. Clinical trial information: NCT02010567. [Table: see text]

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Intensified irinotecan-based neoadjuvant chemoradiotherapy in rectal cancer: Four consecutive designed studies to minimize acute toxicity and to optimize efficacy measured by pathologic complete response

Radiotherapy and Oncology ◽

10.1016/j.radonc.2007.10.042 ◽

2007 ◽

Vol 85 (3) ◽

pp. 379-384 ◽

Cited By ~ 16

Author(s):

Gunther Klautke ◽

Ute Küchenmeister ◽

Thomas Foitzik ◽

Kaja Ludwig ◽

Sabine Semrau ◽

...

Keyword(s):

Rectal Cancer ◽

Acute Toxicity ◽

Pathologic Complete Response ◽

Neoadjuvant Chemoradiotherapy ◽

Complete Response

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How to Combine Diffusion-Weighted and T2-Weighted Imaging for MRI Assessment of Pathologic Complete Response to Neoadjuvant Chemoradiotherapy in Patients with Rectal Cancer?

Korean Journal of Radiology ◽

10.3348/kjr.2020.1403 ◽

2021 ◽

Vol 22 ◽

Author(s):

Jong Keon Jang ◽

Chul-min Lee ◽

Seong Ho Park ◽

Jong Hoon Kim ◽

Jihun Kim ◽

...

Keyword(s):

Rectal Cancer ◽

Pathologic Complete Response ◽

Neoadjuvant Chemoradiotherapy ◽

Complete Response ◽

Diffusion Weighted

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Avoiding Unnecessary Major Rectal Cancer Surgery by Implementing Structural Restaging and a Watch-and-Wait Strategy After Neoadjuvant Radiochemotherapy

Annals of Surgical Oncology ◽

10.1245/s10434-020-09192-0 ◽

2020 ◽

Cited By ~ 1

Author(s):

J. F. Huisman ◽

I. J. H. Schoenaker ◽

R. M. Brohet ◽

O. Reerink ◽

H. van der Sluis ◽

...

Keyword(s):

Rectal Cancer ◽

Locally Advanced ◽

Pathologic Complete Response ◽

Neoadjuvant Chemoradiotherapy ◽

Complete Response ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Response Evaluation ◽

Watch And Wait ◽

Time To Event

Abstract Background Pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) is found in 15–20% of patients with locally advanced rectal cancer. A watch-and-wait (W&W) strategy has been introduced as an alternative strategy to avoid surgery for selected patients with a clinical complete response at multidisciplinary response evaluation. The primary aim of this study was to evaluate the efficacy of the multidisciplinary response evaluation by comparing the proportion of patients with pCR since the introduction of the structural response evaluation with the period before response evaluation. Methods This retrospective cohort study enrolled patients with locally advanced rectal cancer who underwent nCRT between January 2009 and May 2018, categorizing them into cohort A (period 2009–2015) and cohort B (period 2015–2018). The patients in cohort B underwent structural multidisciplinary response evaluation with the option of the W&W strategy. Proportion of pCR (ypT0N0), time-to-event (pCR) analysis, and stoma-free survival were evaluated in both cohorts. Results Of the 259 patients in the study, 21 (18.4%) in cohort A and in 8 (8.7%) in cohort B had pCR (p = 0.043). Time-to-event analysis demonstrated a significant pCR decline in cohort B (p < 0.001). The stoma-free patient rate was 24% higher in cohort B (p < 0.001). Conclusion Multidisciplinary clinical response evaluation after nCRT for locally advanced rectal cancer led to a significant decrease in unnecessary surgery for the patients with a complete response.

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Circulating Biomarkers for Response Prediction of Rectal Cancer to Neoadjuvant Chemoradiotherapy

Current Medicinal Chemistry ◽

10.2174/0929867326666190507084839 ◽

2020 ◽

Vol 27 (25) ◽

pp. 4274-4294 ◽

Cited By ~ 1

Author(s):

Chiara Bedin ◽

Sara Crotti ◽

Edoardo D’Angelo ◽

Sara D’Aronco ◽

Salvatore Pucciarelli ◽

...

Keyword(s):

Rectal Cancer ◽

Clinical Benefit ◽

Locally Advanced ◽

Pathologic Complete Response ◽

Neoadjuvant Treatment ◽

Neoadjuvant Chemoradiotherapy ◽

Treatment Protocol ◽

Predictive Biomarkers ◽

Complete Response ◽

Tumour Regression

: Rectal cancer response to neoadjuvant Chemoradiotherapy (pCRT) is highly variable. In fact, it has been estimated that only about 21 % of patients show pathologic Complete Response (pCR) after therapy, while in most of the patients a partial or incomplete tumour regression is observed. Consequently, patients with a priori chemoradioresistant tumour should not receive the treatment, which is associated with substantial adverse effects and does not guarantee any clinical benefit. For Locally Advanced Rectal Cancer Patients (LARC), a standardized neoadjuvant treatment protocol is applied, the identification and the usefulness of prognostic or predictive biomarkers can improve the antitumoural treatment strategy, modifying the sequence, dose, and combination of radiotherapy, chemotherapy and surgical resection. : For these reasons, a growing number of studies are actually focussed on the discovery and investigation of new predictive biomarkers of response to pCRT. In this review, we have selected the most recent literature (2012-2017) regarding the employment of blood-based biomarkers potentially predicting pCR in LARC patients and we have critically discussed them to highlight their real clinical benefit and the current limitations of the proposed methodological approaches.

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