First toxicity and efficacy analysis of a phase II trial of a novel 5-FU-oxaliplatin based chemoradiation schema for stage II and III rectal carcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14591-14591 ◽  
Author(s):  
E. M. Rishe ◽  
S. Malamud ◽  
K. Hu ◽  
W. Enker ◽  
P. Kozuch ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Neoadjuvant Treatment ◽  
Standard Of Care ◽  
Neoadjuvant Chemoradiation ◽  
Stage Ii ◽  
Efficacy Analysis ◽  
Significant Toxicity ◽  
Grade 3

14591 Background: 5-FU based neoadjuvant chemoradiation (CRT) has become the standard of care for stage 2 and 3 rectal cancer (ca). Pathologic complete responses (pCR) and downstaging have been associated with improved survival outcomes. The addition of oxaliplatin or irinotecan to neoadjuvant treatment has led to improved pCR and downstaging. The feasibility and efficacy of “total” oxaliplatin therapy (pre and postoperative oxaliplatin) for stage 2 and 3 rectal ca patients has yet to be defined. Objective: To determine the feasibility, toxicity and efficacy of neoadjuvant oxaliplatin, 5-FU and RT followed by surgery, with postop adjuvant modified FOLFOX6. Methods: Single institution, single arm phase II trial of oxaliplatin 60mg/m2 weekly for 6 weeks with continuous infusion 5- FU 225 mg/m2/excision. Postoperative therapy consisted of mFOLFOX6 every 2 weeks for 6 cycles. Eligibility included previously untreated, histologically proven rectal cancer, T3–4N0M0 or TanyN+M0 (stage II-III). Results: 15 pts have been enrolled in this study. One died of disease prior to CRT. Eight pts have completed total oxaliplatin therapy. One pt had 1 cycle deleted due to grade 2 neuropathy. Prior to adjuvant therapy 2 pts dropped out: 1 from pulmonary symptoms and one asthenia. Two pts attained a pCR and 6 attained downstaging. Significant toxicity has been limited to grade 3 neuropathy in one pt (completely resolved) and one grade 3 GI toxicity (self limited). Conclusions: Early analysis shows the feasibility of pre and post operative oxaliplatin based therapy. The limited data permit only observation of pCR and tumor downstaging rates but toxicity outcomes are encouraging. Further accrual and follow-up will better define efficacy and toxicity of this regimen. [Table: see text]

A phase II study of complete neoadjuvant therapy in rectal cancer (CONTRE): The Brown University Oncology Group.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 335-335 ◽  
Author(s):  
Kimberly Perez ◽  
Victor Pricolo ◽  
Matthew Vrees ◽  
Thomas A. DiPetrillo ◽  
Nicholas Oldenberg ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Complete Response ◽  
Stage Ii ◽  
R0 Resection ◽  
Pelvic Mri ◽  
Grade 3

335 Background: While preoperative chemoradiation followed by surgery is the standard approach for patients (pts) with newly diagnosed clinical stage II-III rectal cancer, many are unable to tolerate postoperative adjuvant chemotherapy which may compromise disease-free and overall survival. CONTRE is a multicenter phase II study designed to determine the feasibility of administering all chemotherapy prior to surgery and to assess its impact on pathologic complete response (pCR) and complete (R0) resection Methods: Pts with T3-4 and/or N1-2 rectal cancer, staged by endorectal ultrasound (ERUS) and pelvic MRI, receive modified (m) FOLFOX6 every 2 weeks x 8 cycles, followed by repeat MRI and proctoscopy to assess response. Pts then receive 50.4 Gy IMRT with 5-FU 225 mg/m2/day or capecitabine 825mg/m2 BID, 5 days per week during radiation, followed by surgery 4-8 weeks later. Results: Thus far, we have enrolled 36 of a planned 39 pts (median age 58, range 30-79; T2-1, T3-30, T4-2; N1-20, N2-7). 28 of the first 30 (93%) completed 8 cycles of mFOLFOX6. 26 pts have completed chemoradiation while 2 chose to proceed directly to surgery. All patients opted to receive capecitabine during radiation. Grade 3/4 toxicities during chemotherapy and chemoradiation have included diarrhea (16%) and neutropenia (12%), with grade 3 renal and cardiac toxicities reported in one patient each. A clinical complete response after chemotherapy alone was achieved in 3 of 29 (10%). Of the first 21 pts undergoing surgery, pCR has been achieved in 6 (29%) and R0 resections in 100%. Thus far, all pts have been able to undergo sphincter-sparing resections. Study accrual will be completed by the meeting. Conclusions: A larger proportion of stage II-III rectal cancer pts are able to complete mFOLFOX6 (>90% in our cohort) when administered prior to chemoradiation and surgery. Complete neoadjuvant treatment may represent a well-tolerated alternative to the current standard treatment sequence and a platform for the evaluation of novel therapeutics such as targeted agents during preoperative therapy. Funded in part by LIFEcycle, Inc. Clinical trial information: NCT01363843.

Phase II study of preoperative panitumumab, 5-fluorouracil, and oxaliplatin with concurrent radiotherapy in locally advanced rectal cancer: Preliminary safety results (StarPan /STAR-02 Study)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4110-4110
Author(s):  
C. Pinto ◽  
F. Di Fabio ◽  
E. Maiello ◽  
P. Di Tullio ◽  
S. Pini ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Moderate Increase ◽  
Concurrent Radiotherapy ◽  
Grade 3

4110 Background: The aim of this phase II study is to assess the activity of preoperative external radiotherapy combined with panitumumab, oxaliplatin and 5-fluorouracil in locally advanced rectal cancer patients (pts). Methods: Pts entering the study had histologically-proven rectal adenocarcinoma, either uT3N+ or T4 N-/+ stage, with location <12 cm from the anal margin. Panitumumab was administered at a dose of 6 mg/kg IV, 2 weeks before the start of chemoradiotherapy, and then in combination with chemoradiotherapy, every 2 weeks for 3 times. 5-fluorouracil and oxaliplatin were administered according to an established schedule of STAR-01 Study (oxaliplatin 60 mg/m2 IV weekly for six times, and 5- fluorouracil 225 mg/m2/day continuous infusion IV d 1–38). Radiotherapy was delivered up to a dose of 50.4 Gy in daily fractions of 1.8 Gy. Rectal surgery was performed 7–8 weeks after the end of neoadjuvant treatment. Eight courses of adjuvant chemotherapy with FOLFOX4 plus panitumumab at a dose of 6 mg/kg, every 2 weeks, were given after surgery. The primary endpoint of the study was the complete pathological response rate. Results: From February 2007 to December 2008, 35 out of the 55 planned pts were enrolled. Twenty nine pts completed neoadjuvant treatment and 20 underwent surgery (15 pts ongoing). The characteristics of 29 pts were: males 19 (65.5%) and females 10 (34.5%); median age 58 years (range 39–78); median Karnofsky PS 100 (range 70–100); stage: uT3N+ 22 (75.9%), uT4N- 3 (10.3%), uT4N+ 4 (13.8%). The most frequent grade 1–4 side-effects were acneiform rash (96.2%), diarrhea (51.7%) and fatigue (14.3%). Grade 3 diarrhea was registered in 35.7% pts, and grade 3–4 cutaneous toxicity in 51.8%. No grade 3–4 hematological toxicity was found. The median cumulative dose of delivered radiotherapy was 50.4 Gy. The planned dose of panitumumab, 5-fluourouracil and oxaliplatin was administered in 83%, 72% and 67% of pts, respectively. Conclusions: Despite the moderate increase of diarrhea, these early results demonstrate that panitumumab can be safety added to 5-fluorouracil/oxaliplatin-based chemoradiotherapy, without compromising the concurrent radiotherapy dose. No significant financial relationships to disclose.

NSABP FR-2: Phase II study of durvalumab following neoadjuvant chemoRT in stage II-IV rectal cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. TPS727-TPS727
Author(s):  
Thomas J. George ◽  
Greg Yothers ◽  
James J. Lee ◽  
Samuel A. Jacobs ◽  
Melvin Deutsch ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Stage Iv ◽  
Sphincter Preservation ◽  
Stage Ii ◽  
Systemic Steroid ◽  
Clinical Role

TPS727 Background: Locally advanced rectal cancer remains a clinical challenge with few improvements noted over the past few decades. Although immunotherapy has no current clinical role in microsatellite stable (MSS) colorectal cancer, preclinical models suggest that radiotherapy (RT) can enhance neoantigen presentation, modulate the microenvironment, and improve the likelihood of anti-tumor activity with checkpoint inhibitor use. This prospective phase II trial will test that hypothesis in addition to confirming safety of this approach using a “window-of-opportunity” study design with the anti-PD-L1 agent durvalumab (MEDI4736). Methods: This multi-center phase II trial is currently enrolling patients (pts) with rectal cancer who are undergoing standard NCCN guideline-compliant neoadjuvant chemoradiotherapy (CRT). Eligibility includes pts with MSS stage II-IV rectal cancer with adequate organ function and pre-treatment diagnostic tumor available for profiling who are undergoing CRT with intentions to proceed to surgical resection. Stage IV disease must be limited such that the primary pelvic tumor requires definitive management. Standard ineligibility criteria include active infections, systemic steroid use, or other conditions making immunotherapy use unsafe. Treatment includes durvalumab (750mg IV infusion once every 2 wks) for 4 total doses beginning within 3-7 days after CRT completion. Surgery must be within 8-12 wks of the final CRT dose. Primary endpoint is a demonstrated improvement in Neoadjuvant Rectal Cancer (NAR) score compared to historical controls targeting a 20% relative risk reduction in DFS and 3-4% absolute OS improvement. Secondary endpoints include OS, DFS, toxicity, pCR, cCR, therapy completion, negative surgical margins, sphincter preservation, off-target “abscopal” effects for the subset of stage IV pts, and exploratory assessments of tumor infiltrating lymphocytes, circulating immunologic profiles, and molecular predictors of response. A safety run-in phase has completed as a precedent to full enrollment. Enrollment now continues to 47 total pts to achieve 41 surgically evaluable pts. NCT03102047. Support: AstraZeneca-Medimmune, NSABP Foundation Clinical trial information: NCT03102047.

Effect of neoadjuvant chemotherapy and early chemotherapeutic response evaluation for low/intermediated-risk mid-low stage II/III rectal cancer: A prospective, open-label, single-arm, phase II trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16133-e16133
Author(s):  
Xiangbing Deng ◽  
Liang Bi ◽  
Qingbin Wu ◽  
Du He ◽  
Hongfeng Gou ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Likelihood Ratio ◽  
Phase Ii ◽  
Local Control ◽  
Phase Ii Trial ◽  
Stage Ii ◽  
Early Assessment ◽  
Tumor Length ◽  
Chemotherapeutic Response

e16133 Background: Neoadjuvant chemoradiotherapy (NCRT) is the standard of care for stage II/III rectal cancer (RC) for its local-control effect. As advancement in surgery, local relapse was no longer the primary cause of failures, especially in low/intermediated-risk stage II/III RCs, in which benefit of radiotherapy in local control wasn’t shown in our previous trial. Distant relapse has become the major form of recurrences, and occurs at an increased rate when chemotherapy was delayed. This trial explores the effect of neoadjuvant chemotherapy (NCT), and the possibility of early assessment of chemotherapeutic response in low/intermediated-risk stage II/III RCs. Methods: This prospective, single arm, phase II trial planned to enroll 60 low/intermediate-risk stage II/III mid-low RCs (low: cT3a-bN0-1M0 MRF(-); mid: cT3a-c or T4aN0-1M0). 4 cycles of CAPOX NCT were scheduled. Rectal MRI, transanal US, endoscopy, CT were examined prior to treatment and after every two cycles. The primary outcome was the clinicopathological response, defined as pathological TRG0-1, TRG2 without tumor length increase, or TRG3 with tumor length regression over 30%. This study was approved by the Ethics Committees of West China Hospital and registered at ClinicalTrials.gov (NCT03666442). Results: From Dec. 2017 to Oct. 2019, 61 eligible patients were enrolled. Two patients received 3 cycles and 2 had only 2 cycles of chemotherapy due to intolerable adverse effects; 57 cases finished 4 cycles. In pathological evaluation, 13 patients (21.3%) were complete response (pTRG0) with one positive node in one patient; 5 cases were pTRG1; 26 were pTRG2; 17 had no response (pTRG3). 48 cases (78.7%) were responders. In the ROC curve predicting the responder via the 2-cycle regression in tumor length, the AUC was 0.864 (95%CI (0.764,0.963), p < 0.001), and the best cutoff regression rate after 2 cycles NCT was 27%. With this cutoff, the sensitivity was 83.3%; specificity was 84.6%; accuracy was 83.6%; positive likelihood ratio was 5.42; negative likelihood ratio was 0.20. Conclusions: NCT achieve more favorable pCR and tumor response rate in low/intermediated-risk stage II/III RCs, comparing to previous studies. The tumor regression after 2 cycles NCT had good accuracy in diagnosing the chemotherapeutic response. This early assessed chemosensitivity may become another feature for tailored use of neoadjuvant treatments, further cohort study will be conducted. Clinical trial information: NCT03666442 .

Phase II trial of 4 cycles dose dense docetaxel (D) 100mg/m2 every 2 weeks with G-CSF support, followed by 3 cycles of 5-fluorouracil (F), epirubicin (E) and cyclophosphamide (C) every 3 weeks as neoadjuvant treatment of operable > 2cm breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10636-10636
Author(s):  
G. Romieu ◽  
F. Bibeau ◽  
S. Culine ◽  
S. Gourgou-Bourgade ◽  
C. Guillemare ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Neoadjuvant Treatment ◽  
Conservative Surgery ◽  
Treatment Sequence ◽  
Early Stage Disease ◽  
Grade 3 ◽  
Dose Dense

10636 Background: Docetaxel is one of the most active chemotherapy agents used in breast cancer. Given the effectiveness of Taxotere in the treatment of metastatic breast cancer, it is now being extensively evaluated in the treatment of early stage disease. Recently, we initiated in our institution a study, which showed that the bi-weekly administration of 4 cycles of docetaxel was feasible with G-CSF (lenograstim) support. This phase II trial was initiated to evaluate the pCR rate of docetaxel as a single agent followed by FEC 100 in the neoadjuvant setting. Methods: Eligible patients (pts) with histologically proven breast cancer, measurable lesions >2 cm were scheduled to receive 4 cycles of chemotherapy with a day 1 bolus of (D) 100 mg/m2 every 14 days + corticoids for 3 days starting the day before first infusion as premedication and primary prophylaxis with G-CSF: followed by 3 cycles of a continuous infusion of F 500 mg/m2, E 100 mg/m2 and C 500 mg/m2 day 1 (FEC100). The primary endpoint was the pCR rate using the classification of Sataloff. Results: From 12/2003 to 12/2004, we treated 45 pts with median age 45 [25–63]. To date, 43 pts with WHO PS 0 were evaluable with T2: 22, T3: 19, T4: 2 pts and 18/21/5/1 N0/N1/N2/N3. Among 43 eligible pts, 2 stopped because of toxicity (after the 2nd and 4th cycles) and 1 patient refused to continue after 3 cycles. During the first treatment sequence with D, grade 3–4 toxicities (%pts): neutropenia (13), grade 3: cutaneous (24), myalgies (4), and arthalgies (2), and grade 2 neurotoxicity (31). During the second treatment sequence with FEC, grade 3–4 toxicities (% pts) were: neutropenia (95), grade 3: thrombocytopenia (5), myalgies (2), mucitis (2), grade 2 neurotoxicity (24). The conservative surgery rate was 67% and 3 pts needed a secondary mastectomy. The pCR rate was 50% (95% CI 34%– 66%) (26% T-A) among 42 evaluable pts. Conclusion: This regimen allows conservative surgery in more than half of all patients and we conclude from these findings that 4 cycles of dose-dense D followed by 3 cycles of FEC is an active induction regimen with a tolerable toxicity profile. No significant financial relationships to disclose.

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