scholarly journals Neoadjuvant Capecitabine and Oxaliplatin Before Concurrent Capecitabine and Radiation in Locally Advanced Rectal Cancers: Experience of a Cancer Hospital in Pakistan

2021 ◽  
pp. 790-796
Author(s):  
Muhammad Atif Mansha ◽  
Asmara Waheed ◽  
Tabinda Sadaf ◽  
Asma Rashid ◽  
Nabia Irfan ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Circumferential Resection Margin ◽  
Randomized Clinical Trials ◽  
Resection Margin ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Response Rates ◽  
Complete Response ◽  
Grade 3

PURPOSE To report the toxicity and pathologic response rates after adding neoadjuvant capecitabine and oxaliplatin (CAPOX) followed by concurrent radiation and capecitabine (CAPRT) and surgery in patients with locally advanced rectal cancer. MATERIALS AND METHODS We retrospectively analyzed medical records of 301 patients between January 2007 and December 2014. Patients were treated with four cycles of neoadjuvant chemotherapy comprising CAPOX, followed by radiotherapy at doses of 45-54 Gy in 25-30 fractions with concurrent capecitabine. A response assessment scan was performed at 4-6 weeks postradiation followed by surgical evaluation at 6-8 weeks. Pathologic tumor and nodal response rates as well as circumferential resection margin were assessed on surgical specimens. RESULTS The median age of the patients was 43 years (range, 16-78). Overall, 227 (75.4%) patients were able to complete four cycles of CAPOX. Neoadjuvant chemotherapy was well-tolerated with no serious adverse effects. The most common toxicity was diarrhea (grade 2, n = 108; 35.8%; grade 3, n = 57; 18.9%; grade 4, n = 25; 8.3%) followed by neuropathy (grade 2, n = 132; 43.8%; grade 3, n = 54; 17.9%) and oral mucositis (grade 2, n = 108; 35.8%; grade 3, n = 47; 15.6%; grade 4, n = 9; 2.99%). A total of 229 (76.1%) patients underwent surgery. Pathologic complete response was seen in 52 (22.7%; 95% CI, 13 to 28), whereas 200 (87.3%; 95% CI, 82 to 99) patients had a negative circumferential resection margin on pathology. CONCLUSION Neoadjuvant chemotherapy with CAPOX before CAPRT and planned total mesorectal excision surgery result in good tumor regression and substantial pathologic complete response rates with acceptable toxicity. With growing interest in organ preservation in rectal cancer, the strategy of completing all chemotherapy and chemoradiotherapy before planned surgery offers a favorable paradigm. However, further randomized clinical trials are needed to support this evidence.

Phase Ib/II study of neoadjuvant chemoradiotherapy with CRLX101 and capecitabine for locally advanced rectal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15144-e15144 ◽  
Author(s):  
Andrew Wang ◽  
Autumn Jackson McRee ◽  
A. William Blackstock ◽  
Bert H. O'Neil ◽  
Dominic T. Moore ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Single Agent ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Chemoradiotherapy ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Phase Ib ◽  
Grade 3

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]

Outcomes of Neoadjuvant Chemotherapy without Radiation for Rectal Cancer

2015 ◽  
Vol 32 (4) ◽  
pp. 275-283 ◽  
Author(s):  
Takuya Matsumoto ◽  
Suguru Hasegawa ◽  
Masazumi Zaima ◽  
Naoya Inoue ◽  
Yoshiharu Sakai
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Pathological Complete Response ◽  
Locally Advanced ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Short Term ◽  
Group 2 ◽  
Grade 3

Aim: The efficacy of neoadjuvant chemotherapy without radiation (NAC) in the treatment of rectal cancer remains unclear. This retrospective study was aimed at determining the pathological complete response rate and short-term outcomes of NAC in patients with locally advanced rectal cancer. Patients and Methods: We collected data on 159 consecutive patients treated for rectal cancer (cT3/cT4a, cN+, and cM0 status) at five tertiary referral hospitals between 2005 and 2010. Pathological complete response (pCR) and safety were assessed as the main outcomes in 124 eligible patients comprising 15 who received NAC (NAC group) and 109 who received no neoadjuvant chemotherapy (non-NAC group). Results: In the NAC group, 2 patients (13.3%) achieved a pCR (95% confidence interval: 1.7-40.5%) and 3 patients (20%) experienced grade 3/4 adverse events. No significant differences were found between the NAC and non-NAC groups in terms of short-term outcomes, including R0 proportion (100 vs. 96.3%, p = 0.45) and postoperative grade 3/4 complications (13.3 vs. 18.4%, p = 0.63). Conclusions: Neoadjuvant systemic chemotherapy without radiation appears to be safe, without worsening short-term outcomes, in patients with locally advanced rectal cancer. A further study is needed to verify these findings in larger samples.

Capecitabine and oxaliplatin as induction and concomitant with radiotherapy in rectal cancer: A phase II study.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 604-604
Author(s):  
J. A. Gutierrez ◽  
G. Martinez-Martinez ◽  
A. J. Silva ◽  
J. Gomez Rangel ◽  
M. Palmerin ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Performance Status ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Induction Treatment ◽  
Ecog Performance Status ◽  
Dermatologic Toxicity ◽  
Grade 3 ◽  
Experienced Grade

604 Background: Preoperative combined modality chemoradiation with fluoropyrimidine-based schedules is widely accepted as the current standard of care for localized rectal cancer. Current strategies have focused on intensifying the neoadjuvant systemic treatment to improve pCR. Methods: From January 2009 to January 2010, 18 patients with locally advanced rectal cancer (T3, any N, M0) were included according to Simon's design. Treatment was 2 cycles of capecitabine 1000 mg/m2 bid (D1-14) and oxaliplatin 85 mg/m2 (D1) every 3 weeks as induction followed by chemoradiation (45 Gy). During radiotherapy patients received 2 cycles of capecitabine 750 mg/m2 bid (D1-14) and oxaliplatin 85 mg/m2 (D1 and 8) every 3 weeks. Surgery was planned 5-10 weeks after completion of radiotherapy. The primary endpoint was pCR. Results: 18 patients were assessable for response. Median age was 55 y (41-65), 11 patients with ECOG performance status of 1 (61%), all 18 patients were staged as T3, 10 were staged N+ (56%). Of the 18 patients, 17 patients were given CRT and 13 patients (76%) underwent radical resection. Of the patients who did not underwent resection, 1 patient was considered unresectable at the time of surgery, 2 patients refused surgery because of clinical complete response and 1 patient experienced progressive disease to the spine after chemoradiation. During induction treatment 1 patient (6%) experienced grade 3-4 toxicity (diarrhea). During chemoradiation 1 patient (6%) experienced grade 3 diarrhea and nausea and 1 patient (6%) experienced grade 3 radio-induced dermatologic toxicity; overall grade 3-4 toxicity of 12%. No grade 4 toxicity or treatment related deaths were observed. Of the 13 patients who underwent resection, 12 patients (92%) had a complete resection (R0). Pathologic complete response rate was observed in 1 patient (6%) according to intent to treat. The study was closed after the first stage because it did not reach the minimum required number of pCR. Conclusions: Induction chemotherapy with capecitabine and oxaliplatin before chemoradiation is feasible. Given that we did not reach the prespecified pCR rate required to continue the trial, the study was closed after the first stage. No significant financial relationships to disclose.

The safety and tolerability of veliparib (V) plus capecitabine (C) and radiation (RT) in subjects with locally advanced rectal cancer (LARC): Results of a phase 1b study.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 579-579 ◽  
Author(s):  
Brian G. Czito ◽  
Mary Frances Mulcahy ◽  
Dustin A. Deming ◽  
Houman Vaghefi ◽  
Gayle S. Jameson ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Parp Inhibitor ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Post Surgery ◽  
Tumor Downstaging ◽  
Grade 3 ◽  
Dose Proportional

579 Background: Patients (pts) with LARC treated with neoadjuvant C/RT and then surgery have low rates of pathologic complete response (ypCR) and significant relapse rates. V is a potent, orally bioavailable PARP inhibitor that has been shown to enhance the efficacy of chemotherapy and RT in preclinical models. This study sought to establish the recommended phase 2 dose (RPTD), as well as to assess safety, pharmacokinetics (PK), and preliminary activity of V + RT/C in pts with LARC. Methods: Pts with stage II-III rectal cancer received RT (50.4Gy/1.8Gy/fraction) with C (825 mg/m2 BID) five days per week (W) for 5.5W. Dosing of V (BID, 20mg-400mg) continued from W1D2 to 2 days past RT. Pts underwent surgery 5-10W following RT. Assessments included identification of RPTD with the Exposure Adjusted Continual Reassessment Method, adverse events (AEs), PK, and pathological response (ypCR and tumor downstaging rates). Results: As of August 5, 2014, 30 pts have been enrolled, 24/6 male/female, median age 58 yrs; 1 pt discontinued due to an AE. The most common treatment-emergent AEs possibly or probably related to V (>15% pts, n >4) were nausea (40%), fatigue (37%), diarrhea (30%), vomiting (20%), and dysgeusia (17%). One grade 3/4 event each of anemia and lymphopenia and 2 grade 3/4 events of diarrhea were deemed at least possibly related to V. Two dose limiting toxicities (DLTs) occurred: 1 at 70 mg BID V (radiation skin injury requiring dose interruption); 1 at 400 mg BID (nausea and vomiting requiring discontinuation). The RPTD is 400 mg BID of V in combination with RT/C. PK results from 16 pts suggest that V PK was approximately dose proportional when administered with RT/C and that V had no effect on the PK of C. To date, 18/25 (72%) pts have been downstaged post-surgery; with 7/25 (28%) achieving ypCR. Conclusions: V at 400 mg in combination with RT/C has an acceptable safety profile. 72% of 25 evaluable patients had tumor downstaging post-surgery, including 28% with ypCR. Dose escalation of V resulted in approximately dose-proportional increases in the V PK with no clear effect on C PK. Clinical trial information: NCT01589419.

Phase I/II Trial of Capecitabine, Oxaliplatin, and Radiation for Rectal Cancer

2003 ◽  
Vol 21 (16) ◽  
pp. 3098-3104 ◽  
Author(s):  
Claus Rödel ◽  
Gerhard. G. Grabenbauer ◽  
Thomas Papadopoulos ◽  
Werner Hohenberger ◽  
Hans-Joachim Schmoll ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Sphincter Preservation ◽  
Phase Iii ◽  
Grade 3

Purpose: The purpose of this study was to establish the feasibility and efficacy of preoperative radiotherapy (RT) with concurrent capecitabine and oxaliplatin (XELOX-RT) in patients with rectal cancer. Patients and Methods: Thirty-two patients with locally advanced (T3/T4) or low-lying rectal cancer received preoperative RT (total dose, 50.4 Gy). Capecitabine was administered concurrently at 825 mg/m2 bid on days 1 to 14 and 22 to 35, with oxaliplatin starting at 50 mg/m2 on days 1, 8, 22, and 29 with planned escalation steps of 10 mg/m2. End points of the phase II study included downstaging, histopathologic tumor regression, resectability of T4 disease, and sphincter preservation in patients with low-lying tumors. Results: Dose-limiting grade 3 gastrointestinal toxicity was observed in two of six patients treated with 60 mg/m2 of oxaliplatin. Thus, 50 mg/m2 was the recommended dose for the phase II study. Toxicities observed at this dose level were generally mild, with only two cases of short-lived grade 3 diarrhea. Myelosuppression, mainly leukopenia, was restricted to grade 2 in 19% of patients. T-category downstaging was achieved in 17 (55%) of 31 operated patients, and 68% of patients had negative lymph nodes. Pathologic complete response was found in 19% of the resected specimens. Radical surgery with free margins could be performed in 79% of patients with T4 disease, and 36% of patients with tumors ≤ 2 cm from the dentate line had sphincter-saving surgery. Conclusion: Preoperative XELOX-RT is a feasible and well tolerated treatment. This regimen is proposed for phase III evaluation comparing standard fluorouracil-based therapy with XELOX chemoradiotherapy.

scholarly journals Total neoadjuvant treatment of locally advanced rectal cancer with high risk factors in Slovenia

2019 ◽  
Vol 53 (4) ◽  
pp. 465-472
Author(s):  
Mojca Tuta ◽  
Nina Boc ◽  
Erik Brecelj ◽  
Mirko Omejc ◽  
Franc Anderluh ◽  
...  
Keyword(s):  
Risk Factors ◽  
Rectal Cancer ◽  
High Risk ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Complete Response ◽  
Distant Recurrence ◽  
High Risk Factors ◽  
Grade 3

Abstract Background In the light of a high rate of distant recurrence and poor compliance of adjuvant chemotherapy in high risk rectal cancer patients the total neoadjuvant treatment was logical approach to gaining acceptance. We aimed to evaluate toxicity and efficiency of this treatment in patients with rectal cancer and high risk factors for local or distant recurrence. Patients and methods Patients with rectal cancer stage II and III and with at least one high risk factor: T4, presence of extramural vein invasion (EMVI), positive extramesorectal lymph nodes or mesorectal fascia (MRF) involvement were treated with four cycles of induction CAPOX/FOLFOX, followed by capecitabine-based radiochemotherapy (CRT) and two consolidation cycles of CAPOX/FOLFOX before the operation. Surgery was scheduled 8–10 weeks after completition of CRT. Results From November 2016 to July 2018 66 patients were evaluable. All patients had stage III disease, 24 (36.4%) had T4 tumors, in 46 (69.7%) EMVI was present and in 47 (71.2%) MRF was involved. After induction chemotherapy, which was completed by 61 (92.4%) of patients, radiologic downstaging of T, N, stage, absence of EMVI or MRF involvement was observed in 42.4%, 62.1%, 36.4%, 69.7% and 68.2%, respectively. All patients completed radiation and 54 (81.8%) patients received both cycles of consolidation chemotherapy. Grade 3 adverse events of neoadjuvant treatment was observed in 4 (6%) patients. Five patients rejected surgery, 3 of them with radiologic complete clinical remissions. One patient did not have definitive surgery of primary tumor due to unexpected cardiac arrest few days after sigmoid colostomy formation. Among 60 operated patients pathological complete response rate was 23.3%, the rate of near complete response was 20% and in 96.7% radical resection was achieved. Pathological T, N and stage downstaging was 65%, 96.7% and 83.4%, respectively. Grade ≥ 3 perioperative complications were anastomotic leakage in 3, pelvic abscess in 1 and paralytic ileus in 2 patients. The rate of pathologic complete response (pCR) in patients irradiated with 3D conformal technique was 12.1% while with IMRT and VMAT it was 37% (p < 0.05). Hypofractionation with larger dose per fraction and simultaneous integrated boost used in the latest two was the only factor associated with pCR. ConclusionsTotal neoadjuvant treatment of high risk rectal cancer is well tolerated and highly effective with excellent tumor and node regression rate and with low toxicity rate. Longer follow up will show if this strategy will improve distant disease control and survival.

scholarly journals Mutational and Clinical Predictors of Pathologic Complete Response in the Treatment of Locally Advanced Rectal Cancer

2013 ◽  
Vol 45 (1) ◽  
pp. 34-39 ◽  
Author(s):  
Andrea L. Russo ◽  
David P. Ryan ◽  
Darrell R. Borger ◽  
Jennifer Y. Wo ◽  
Jackie Szymonifka ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Clinical Predictors

scholarly journals The Prognostic Impact of Body Composition for Locally Advanced Breast Cancer Patients Who Received Neoadjuvant Chemotherapy

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 608
Author(s):  
Toshiaki Iwase ◽  
Aaroh Parikh ◽  
Seyedeh S. Dibaj ◽  
Yu Shen ◽  
Tushaar Vishal Shrimanker ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Composition ◽  
Adipose Tissue ◽  
Neoadjuvant Chemotherapy ◽  
Advanced Breast Cancer ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Advanced Breast

Our previous study indicated that a high amount of visceral adipose tissue was associated with poor survival outcomes in patients with early breast cancer who received neoadjuvant chemotherapy. However, inconsistency was observed in the prognostic role of body composition in breast cancer treatment outcomes. In the present study, we aimed to validate our previous research by performing a comprehensive body composition analysis in patients with a standardized clinical background. We included 198 patients with stage III breast cancer who underwent neoadjuvant chemotherapy between January 2007 and June 2015. The impact of body composition on pathologic complete response and survival outcomes was determined. Body composition measurements had no significant effect on pathologic complete response. Survival analysis showed a low ratio of total visceral adipose tissue to subcutaneous adipose tissue (V/S ratio ≤ 34) was associated with shorter overall survival. A changepoint method determined that a V/S ratio cutoff of 34 maximized the difference in overall survival. Our study indicated the prognostic effect of body composition measurements in patients with locally advanced breast cancer compared to those with early breast cancer. Further investigation will be needed to clarify the biological mechanism underlying the association of V/S ratio with prognosis in locally advanced breast cancer.

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