Neoadjuvant cetuximab, capecitabine, and radiotherapy (RT) in locally advanced resectable rectal cancer: results of a phase II trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15029-e15029
Author(s):  
V. Velenik ◽  
J. Ocvirk ◽  
I. Oblak ◽  
F. Anderluh
Keyword(s):  
Rectal Cancer ◽  
Phase Ii ◽  
Tumor Regression ◽  
Anal Verge ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Sphincter Preservation ◽  
Open Label ◽  
Resectable Rectal Cancer ◽  
Grade 3

e15029 Background: Preoperative chemoradiotherapy (CRT) with capecitabine is a treatment of choice for locally advanced rectal cancer. The radiosensitizing effect of cetuximab, an EGFR-targeting monoclonal antibody, may further enhance the tumor response. The aim of this prospective, nonrandomized, open-label phase II study was to establish the efficacy and safety profile of cetuximab combined with capecitabine and concurrent RT for locally advanced resectable rectal cancer. Methods: Patients (pts) with stage II or III rectal cancer confirmed by MRI were treated with capecitabine 1250 mg/m2 twice daily for 2 weeks. Cetuximab 400mg/m2 was intravenously administered on week 3, followed by cetuximab 250mg/m2/week and capecitabine 825 mg/m2 bid including weekends during RT. The RT dose was 45 Gy (25×1.8 Gy, 3D conformal technique), starting on week 4. Total mesorectal excision was scheduled 4–6 weeks after completion of CRT. Tumor regression grades (TRG) were evaluated on surgical specimens according to Dworak. The primary endpoint was complete pathologic response (pCR). Results: Thirty-seven pts were eligible for safety and efficacy analyses. Median age was 55 (range: 33–72) years, 81% of pts were male. Three pts (8.1%) had T3N0 tumors, 1 pt (2.7%) T2N1, 13 pts (35%) T3N1, 1 pt (2.7%) T2N2, 15 pts (40.5%) T3N2 and 4 pts (11%) T4N2. The median tumor distance from anal verge was 6 (range: 1–11) cm. All pts received 45 Gy RT. Dose reduction/treatment interruption was necessary for 9/37 (24.3%) pts owing to hypersensitivity reaction (n=4), hepatotoxicity grade 3 (n=1) or diarrhea grade 3 (n=4). Other grade 3 toxicities included dermatitis (n=6, 16.2%), anorexia (n=1, 2.7%) and infection (n=1, 2.7%). TRG 4 (pCR) was recorded in 3 pts (8.1%) and TRG 3 in 7 pts (18.9%). T-, N- and overall downstaging rates were 56.8%, 81.1% and 73.0%, respectively. The total sphincter preservation rate was 75.7%; in 17 pts whose tumors were located ≤5 cm of the anal verge, the rate was 53%. Conclusions: Preoperative CRT with cetuximab and capecitabine is safe and feasible. A high pathologic downstaging rate was achieved, although the pCR rate appeared to be in the range previously reported for CRT with capecitabine. No significant financial relationships to disclose.

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.

Phase II study of preoperative chemoradiation (CRT) with cetuximab, irinotecan and capecitabine in patients with locally advanced resectable rectal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4045-4045 ◽  
Author(s):  
Y. S. Hong ◽  
D. Y. Kim ◽  
K. S. Lee ◽  
S. B. Lim ◽  
H. S. Choi ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Anal Verge ◽  
Locally Advanced ◽  
Rectal Adenocarcinoma ◽  
R0 Resection ◽  
Efficacy And Safety ◽  
Open Label ◽  
Resectable Rectal Cancer

4045 Background: Preoperative CRT with irinotecan and capecitabine is effective and safe in rectal cancer. Cetuximab, an EGFR- targeted agent, is synergistic with chemotherapy and radiotherapy. We conducted this study to determine efficacy and safety of cetuximab, irinotecan, and capecitabine as a combined preoperative CRT in patients with locally advanced resectable rectal cancer. Methods: This is a non-randomized, open-label, multicenter phase II study with cetuximab 400mg/m2 on D-6 (1 week before radiation) followed by cetuximab 250mg/m2 and irinotecan 40mg/m2 once a week (D1, 8, 15, 22, & 29) and capecitabine 1650mg/m2/day for weekdays only during radiation. Radiotherapy was given to a total dose of 50.4 Gy/28 fractions starting on D1. Main eligibility criteria were histologically proven rectal adenocarcinoma; T3–4 lesions; age 18 - 75 years; ECOG PS 0 - 2; no prior chemotherapy or EGFR targeted therapy. Total mesorectal excision was planned to be performed 4–8 weeks after completion of CRT. Results: Between May 2006 and Dec 2006, 40 patients were enrolled; median age 56.5 years (34 - 72); M/F 32/8; PS 0–1/2 38/2; cT3/T4 36/4; cN0/N+ 8/32; median tumor location from anal verge 5.5cm (0 - 8.0); moderately-differentiated adenocarcinoma 29. At present, 21 patients completed preoperative CRT and were evaluable for toxicity. Grade 3/4 toxicities included leucopenia (2, 9.5%), neutropenia (1, 4.8%), anemia (1, 4.8%) and diarrhea (1, 4.8%). Grade 2 hypersensitivity reactions and skin rashes were observed in 2 (9.5%) and 9 patients (42.9%), respectively and no grade >1 hand-foot syndrome was observed. Of 10 patients who underwent surgery (all R0 resection) till now, 9 were treated with sphincter saving procedure. Pathologic T0 and N0 were observed in 3 and 7 patients, respectively. Pathologic complete responses were observed in 2 patients and another 2 patients had only minimal microscopic residual tumor. Conclusions: Preoperative CRT with cetuximab, irinotecan and capecitabine showed promising preliminary pathologic responses with mild toxicity profiles. Study enrollment has now been completed and further results of efficacy and safety will be presented. No significant financial relationships to disclose.

Concurrent radiotherapy (RT) and chemotherapy (CT) with oxaliplatin as primary treatment of advanced rectal cancer: a phase II study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13507-13507 ◽  
Author(s):  
A. Alberti ◽  
F. Tomei ◽  
E. Miele ◽  
N. Pizzardi ◽  
S. Ramponi ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Total Dose ◽  
Sample Size ◽  
Phase Ii ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Sphincter Preservation ◽  
Pathological Response ◽  
Tumor Bed ◽  
Concomitant Boost

13507 Background: Combined pre-operative RT and CT increase the possibility for conservative surgery in locally advanced rectal cancer. Most clinical trials show that responding patients could obtain a reduction of local relapse and an improvement of overall survival, especially when a complete pathological response is obtained (pCR 9–29%). The aim of our study was to determine the activity of RT concomitant to oxaliplatin (OHP) in combination with c.i. 5-fluorouracil (5FU). Methods: Primary endpoint was pCR. Sample size was defined according to Simon Two-Stage phase II design (planned sample size: 29 evaluable patients). From May 2002 to November 2005, 33 patients (15 males, 18 females) were enrolled: median age was 64 years (range 21–74); clinical stage was cT3/cT4 cN0 or cTany cN+ M0. In 24 patients rectal cancer was ≤ 5 cm from anal verge. Weekly OHP 60 mg/m2 was administered in combination with c.i. 5FU 225 mg/ m2 for 5 days per week. Twelve patients received conventional RT (CRT): 25 fractions with 1.8 Gy, total dose 50.4 Gy on the pelvis and a boost on tumor bed with 3 fractions of 1.8 Gy. 21 patients received hyperfractionated RT (HRT): 1.2 Gy b.i.d. for 5 days per week for 4 weeks and a concomitant boost on tumor bed with daily 3 Gy (total dose 54–56 Gy on tumor bed, 48–50 Gy on the pelvis). Patients underwent surgery after 6–8 weeks from the end of treatment. Results: All patients were evaluable for pathological response. Sphincter preservation was obtained in 30 patients (=90.9%), a clinical down-staging in 30 patients (=90.9%). Overall, 12 patients (=36.4%) experienced a pCR: 9 of 21 patients (=42.8%) who received HRT obtained a pCR; 3 of 12 patients (=25%) who received CRT showed a pCR. Treatment was well tolerated. No G3–4 toxicity was observed. Conclusions: The results of our study are promising in terms of sphincter preservation, clinical down-staging and pCR. Moreover in this trial patients who received HRT obtained an encouraging outcome. No significant financial relationships to disclose.

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.

A randomized phase II study of capecitabine-based chemoradiation with or without bevacizumab in resectable locally advanced rectal cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3571-3571 ◽  
Author(s):  
Mercedes Martinez Villacampa ◽  
Jaume Capdevila ◽  
Jose Luis Manzano ◽  
Carles Pericay ◽  
Ramon Salazar ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Correct Selection ◽  
Randomized Phase Ii ◽  
Grade 3 ◽  
The Impact

3571 Background: The addition of bevacizumab (BEV) to capecitabine (CAP)-based chemoradiation (CRT) has shown encouraging efficacy in locally advanced rectal cancer (LARC), in nonrandomized studies. This randomized phase II study investigated the effect of adding BEV to preoperative CAP-based CRT in patients (pts), with LARC. Methods: The primary end point was pathologic complete response (pCR). A two-stage design was used. Assuming a minimum pCR rate of at least 15% in one of the arms, a difference between the two arms of 10%, and accepting a probability of correct selection of 87%, 41 pts per arm were needed. Patients with LARC (Stages II-III assessed by MRI) and ECOG PS <2 were randomized to concurrent radiotherapy 45Gy/25f/5 weeks + CAP (825mg/m²/bid) + BEV every 2 weeks (5 mg/kg for 3 doses) (arm A) or the same schedule without BEV (arm B). Surgery was scheduled 6-8 weeks after completing CRT. Results: 90 pts were randomized (arm A/B: 44/46). Patient’s characteristics were well balanced between both arms: male 61%, median age 62 years, median distance from anal verge 7 cm, T3 79%, N+ 87%. 40 (91%)/43 (93%) of pts (arm A/B) finalized the planned CRT + surgery treatment. Overall grade 3-4 toxicity rates were 18 % and 13% (arm A/B, p=0.50); no grade 3-4 hematological toxicity was reported. Postoperative complications were 19(43%)/17(37%)(arm A/B). Efficacy data on patients who actually underwent surgery are reported in the table. Conclusions: The addition of BEV to CAP-based preoperative CRT has shown to be feasible and safe in the local control of LARC. No differences in pCR were observed and longer follow-up is needed to assess the impact on survival endpoints. [Table: see text]

Voltage: Investigator-initiated clinical trial of nivolumab monotherapy and subsequent radical surgery following preoperative chemoradiotherapy in patients with microsatellite stable locally advanced rectal cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3606-3606 ◽  
Author(s):  
Takayuki Yoshino ◽  
Hideaki Bando ◽  
Yuichiro Tsukada ◽  
Koji Inamori ◽  
Satoshi Yuki ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Rectal Cancer ◽  
Phase I ◽  
Phase Ii ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Fisher Exact Test

3606 Background: Chemoradiotherapy (CRT) with surgery (S) is standard for patients (pts) with locally-advanced rectal cancer (LARC), and nivolumab (nivo) is active in microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). We studied nivo and radical S following CRT (50.4 Gy with capecitabine 1,650 mg/m2) in T3–4 NanyM0 LARC. Methods: Phase I included testing of a recommended phase II dosing schedule (RP2S). Efficacy and safety were studied in phase II pts and those given RP2S in phase I. In Cohort A-1, for microsatellite stable (MSS) LARC pts, the primary endpoint was centrally confirmed pathologic complete response (pCR) rate using AJCC tumor regression grading. The estimated required sample size assuming null and alternative hypotheses pCR = 10% and 30% was 37 pts, with a 1-sided alpha of 5% and power of 90%. Cohort A-2 was exploratory and included a maximum of 5 MSI-H pts. Results: Nivo 240 mg q2 weeks x 5 cycles, following CRT but pre-S, was the RP2S. From 1/17 to 6/18, 37 pts were enrolled in Cohort A-1. Eleven pts (30%; 90% CI 18-44%) showed pCR (AJCC grade (gr) 0). Including the 3 pts (8%) graded AJCC 1, 14 (38%) had major pathologic responses. In addition, clinical CR was observed in 1 pt (3%) refusing S after nivo. Both MSI-H LARC Cohort A-2 pts showed pCRs. Immune-related severe adverse events were observed in 2 pts (gr 3 myasthenia and gr 2 interstitial nephritis); both fully recovered and had S. No treatment-related deaths were observed. pCR rates of 60% (6/10) and 19% (5/27) (p = 0.038, Fisher exact test) were seen in pts with tumor cells with PD-L1 ≥1% and < 1% IHC staining, respectively, performed on biopsy samples taken pre-CRT. Rates of 62% (8/13) and 10% (1/10) (p = 0.029) were seen in 23 pts with samples analyzable by flow cytometry, according to CD8+ lymphocyte /regulatory T cell (CD8/Treg) ratios ≥2 and < 2, respectively. Conclusions: A promising pCR rate of 30%, with mild toxicity, was shown in MSS LARC pts treated with nivo plus radical S. PD-L1 expression and elevated CD8/Treg ratio may be better predictors of nivo benefit, warranting further study in a larger cohort. Clinical trial information: NCT02948348.

Radiotherapy plus concurrent irinotecan (CPT-11) and capecitabine (CAP) as preoperative downstaging treatment for locally advanced inoperable rectal cancer: A phase I/II study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13519-13519 ◽  
Author(s):  
S. W. Gollins ◽  
S. Myint ◽  
E. Levine ◽  
J. Bishop ◽  
B. Haylock ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase Ii ◽  
Anal Verge ◽  
Locally Advanced ◽  
Distant Metastases ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Maximum Tolerated Dose ◽  
Recommended Dose ◽  
Defunctioning Stoma

13519 Background: Preoperative downstaging chemoradiation has become standard treatment for locally advanced unresectable rectal cancer. Oral CAP is potentially more convenient as a radiation sensitiser than infusional fluoropyrimidine regimes. This study evaluated the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended dose (RD) of daily CAP plus weekly i.v. CPT-11 when used in combination with RT in locally advanced rectal cancer. Methods: Patients had an adenocarcinoma of the rectum (lower limit within 12 cm of the anal verge) which on MRI was T3 within 2 mm of the mesorectal outer edge, T4, or any T3 within 5 cm of the anal verge. There were no distant metastases on staging investigations. Patients received planned pelvic RT to 45 Gy in 25 daily fractions over five weeks, concurrent with oral CAP daily throughout RT (including weekends) and a 60 minute infusion of i.v. CPT-11 weeks 1, 2, 3 and 4. Doses of CAP and CPT-11 were gradually escalated in cohorts of three patients. Results: The most common DLT was diarrhoea. Initially dose level (D/L) 3 was chosen as the recommended dose for phase II. However, unacceptable toxicity was encountered in the first 12 patients treated at D/L 3 (see Table). Thus D/L 2 is now being expanded to 60 patients for phase II. 40 patients have thus far potentially been eligible for resection: 5 (13%) could not be resected (2 deteriorated, 2 developed metastases, 1 died during treatment), 32 (80%) had R0 and 3 (7%) R1 resection. 9 (25%) had a pathological complete response (pCR) and 7 (20%) ‘near’ pCR. 5 (9%) of 57 patients had a defunctioning stoma pre-RT. Conclusions: The RD for this regime is 60 mg/m2 i.v. CPT-11 weeks 1, 2, 3, 4 and 650 mg/m2 bd of oral CAP daily. This demonstrates promising signs of efficacy. The RD is currently being studied in an expanded phase II cohort of 60 patients. D=diarrhea; F=febrile neutropenia; A=anorexia; L=lethargy; N=nausea/vomiting. [Table: see text] No significant financial relationships to disclose.

A phase II study of capecitabine plus concomitant radiation therapy followed by durvalumab (MEDI4736) as preoperative treatment in rectal cancer: PANDORA study first-stage.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3607-3607
Author(s):  
Stefano Tamberi ◽  
Elisa Grassi ◽  
Jody Corbelli ◽  
Giorgio Papiani ◽  
Maria aurelia Barbera ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Adverse Events ◽  
Neoadjuvant Therapy ◽  
Phase Ii ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Preoperative Treatment ◽  
Open Label ◽  
Multi Centre Study ◽  
Grade 3

3607 Background: The combination of capecitabine plus long course radiotherapy (RT) is the standard preoperative therapy in cT3-4 cN+ rectal cancer. Pathologic Complete remission (pCR) can be considered as surrogate end point of efficacy of treatment in terms of disease free survival (DFS). Preclinical data points heavily toward a strong synergy between RT and immune treatments. Methods: This is a prospective phase II, open label, single arm, multi-centre study, conducted with support from AstraZeneca, in patient with locally advanced rectal cancer who receive concomitant CT/RT therapy (825 mg/m2 twice daily capecitabine every day and 5040 cGy radiotherapy for 5 days per week for 5 weeks) followed by durvalumab (1500 mg Q4W for 3 administrations). Surgery is performed after 10-12 weeks from neoadjuvant therapy. The primary endpoint is pCR rate after at least 1 cycle of durvalumab. The sample size has been estimated by using the optimal Simon’s two-stage design. If more than 4 complete responses are observed in the first 19 enrolled patients, 36 additional patients will be accrued for a total of 55 evaluable patients. Results: Between November 2019 and July 2020, 20 patients were accrued and 19 were evaluable for study objectives, concluding the first stage of the trial. Baseline characteristics of the first 19 evaluable patients enrolled are listed in the table. All patients received 3 infusions of durvalumab; 18 patients underwent surgery after a median of 13 weeks from CHT/RT end. Five complete pathological responses (ypT0N0) were observed, allowing to proceed to the second stage. About toxicity, four patients had Grade 3-4 adverse events (AE); the most frequent G3-4 AE related to the neoadjuvant therapy were anemia (n=1), diarrhea (n=2) and neuthropenia (n=2). No grade 3 and 4 adverse events related to Durvalumab treatment were observed. Eight patients had G1-2 AE related to durvalumab, the most common being asthenia (n=2) and nausea (n=2). Conclusions: At the end of study’s first stage the preoperative treatment with radiotherapy plus capecitabine followed by durvalumab showed a safe toxicity profile and promising activity in terms of pCR rate. The second part of the trial is ongoing, and the accrual is under completion (44 patients enrolled as of 10 February 2021). Clinical trial information: NCT04083365. [Table: see text]

Preoperative Concurrent Chemoradiotherapy in Locally Advanced Rectal Cancer With High-Dose Radiation and Oxaliplatin-Containing Regimen: The Lyon R0–04 Phase II Trial

2003 ◽  
Vol 21 (6) ◽  
pp. 1119-1124 ◽  
Author(s):  
Jean-Pierre Gérard ◽  
Olivier Chapet ◽  
Chantal Nemoz ◽  
Pascale Romestaing ◽  
Françoise Mornex ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
High Dose ◽  
Operative Specimen ◽  
Concomitant Boost ◽  
Grade 3

Purpose: The combination of radiation, fluorouracil, and oxaliplatin in locally advanced rectal cancer has been shown to be feasible in a phase I trial. The purpose of this phase II trial was to assess tolerance and efficacy of this regimen in a preoperative setting. Patients and Methods: Between May 2000 and October 2001, 40 operable patients were entered onto the study. Radiotherapy was delivered with a three-field technique to a dose of 50 Gy over 5 weeks with a concomitant boost approach. Two cycles of chemotherapy were given synchronously on weeks 1 and 5, with oxaliplatin 130 mg/m2 on day 1 followed by 5-day continuous infusion of fluorouracil 350 mg/m2 and l-folinic acid 100 mg/m2. Surgery was planned 5 weeks later. Results: All patients completed treatment without modification except one who experienced grade 3/4 toxicity. Grade 3 toxicity was seen in seven patients. Surgery was performed in all patients after a mean interval time of 5 weeks. An objective clinical response was seen in 30 patients (75%). Sphincter-saving surgery was possible in 26 patients. No postoperative deaths occurred. In four patients (10%), a reoperation was necessary (anastomotic fistula, n = 2; pelvic abscess, n = 2). In six cases the operative specimen was sterilized (15%), and in 12 cases (30%), only few residual cells were detected. Conclusion: Such a combined preoperative chemoradiotherapy and oxaliplatin-containing regimen is well tolerated with no increase in surgical toxicity. The good response rate observed warrants its use in further clinical trials.

scholarly journals Phase II study of preoperative bevacizumab, capecitabine, and radiotherapy for resectable locally advanced rectal cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 516-516 ◽  
Author(s):  
M. Martinez Villacampa ◽  
C. Santos ◽  
M. García ◽  
V. Navarro ◽  
A. Teule ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Sphincter Preservation ◽  
R0 Resection ◽  
Treatment Schedule ◽  
Preoperative Treatment

516 Background: Bevacizumab into chemoradiotherapy appears safe and active in locally advanced rectal cancer (LARC).This study evaluates whether the addition of bevacizumab to capecitabine-based chemoradiotherapy in the preoperative treatment of LARC improves pathological complete response rate (pCR). Methods: Open-label, unicentric, phase II study in patients with resectable LARC (stage II or III), with or without nodal involvement and no evidence of distant metastases. Treatment schedule of 4-cycles: bevacizumab administered iv on day 1 (10 mg/kg in the first cycle and 5 mg/kg in the following 3 cycles) and capecitabine (900mg/m2/bid) in the 2nd cycle (5 d/wk) concomitantly with radiotherapy 45Gy (25 fractions of 1.8Gy/day) over 5 weeks. Surgical resection was scheduled 6-8 weeks after therapy completion. Preliminary results from ITT analysis are presented. Results: Of the 43 patients included, 41 comprised ITT population. Baseline characteristics: median age 63 (55-67) years; male 76%; ECOG 0/1 49%/51%; stage T3/N1 80.5%/58.5%; nodal metastases 85%. 39 patients underwent surgery, 9 abdominoperineal and 30 anterior resection. No evidence of metastasis after surgery in 97%. Total mesorectal excision was performed in 69% of patients and 85% underwent R0 resection. Sphincter-preservation was achieved in 79.5%. Downstaging occurred in 82%. Among 39 patients evaluable for pathological response, 7.7% experienced pCR, 69.2% partial response and 20.5% stable disease. Grade 3/4 toxicities: 9.8% lymphopenia (all related to capecitabine and 4.9% to bevacizumab), 2.4% neutropenia (capecitabine-related), 2.4% radiodermatitis (related to RT and capecitabine) and 2.4% vasospastic angina (bevacizumab and capecitabine-related). 13 patients had postoperative complications not treatment-related. The most common were wound infection (6), intra-abdominal collection (3), wound dehiscence (2) and paralytic ileus (2). Conclusions: Preoperative regimen with bevacizumab, capecitabine and RT is active for LARC with promising results of R0 resection, sphincter- preservation and tumour downstaging as well as manageable toxicity. Further studies are ongoing to confirm these data. No significant financial relationships to disclose.

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