Safety results of a phase III randomized trial of adjuvant treatment with 5- fluorouracil and folinic acid with or without irinotecan, in Dukes B2 and C colon cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4053-4053 ◽  
Author(s):  
P. Papakostas ◽  
H. P. Kalofonos ◽  
G. Pentheroudakis ◽  
E. Timotheadou ◽  
C. Papadimitriou ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Folinic Acid ◽  
Adjuvant Treatment ◽  
Safety Data ◽  
Phase Iii ◽  
Severe Neutropenia ◽  
Severe Diarrhea ◽  
Number Of Patients ◽  
Group A ◽  
Grade 3

4053 Background: The aim of our phase III study was to compare the effectiveness and the toxicity profile of 5-Fluorouracil (5- FU) + folinic acid (FA) + irinotecan (CPT-11) as adjuvant chemotherapy for resectable colon cancer (Dukes B2 and C) to that of 5-FU + FA which was considered the standard treatment. Since patients are still on follow-up regarding the primary endpoint, only safety results will be presented. Methods: Eligible patients received either 5-FU (450 mg/m2 bolus) + FA (200 mg/m2, 120 min infusion) + CPT- 11 (80 mg/m2, 90 min infusion) given 4 weeks on, two weeks off for a total of 6 treatment cycles (Arm A) or 5-FU (500 mg/m2 bolus) + FA (200 mg/m2, 120 min infusion) given 6 weeks on, two weeks off for a total of 4 treatment cycles (Arm B). Results: From January 1999 to September 2004, 910 patients (pts) were enrolled in this multi-center phase III trial. Safety data are available for 826 of the 910 pts, (415 in arm A and 411 in arm B). The total number of chemotherapy courses delivered was 8,906 (92%) in arm A and 8,775 (91%) in arm B, with median courses per patient 24 in both groups. Among patients who received treatment as randomized (403 in arm A and 398 in arm B), treatment was completed in 342 pts (82%) in arm A and in 341 pts (83%) in arm B. The number of patients who discontinued the treatment was 61 (15%) in arm A and 57 (14%) in arm B. Hospitalizations because of toxic effects happened in 37 pts (9%) in arm A and in 45 pts (11%) in arm B. Three deaths occurred in both arms. Use of G-CSF was more common in arm A (94 pts, 23%) than in arm B (38 pts, 9.5%) (p< 0.001). Significantly higher grade 3/4 neutropenia was observed in group A (11% in arm A and 3% in arm B, p< 0.001). Severe diarrhea was also frequently reported in both groups. Conclusions: These data show that both regimens have comparable and manageable toxicity profiles as adjuvant treatment in colon cancer. Severe neutropenia was more often seen in arm A. No significant financial relationships to disclose.

Adjuvant paclitaxel followed by oral fluoropyrimidines for gastric cancer: Safety data of the factorial phase III SAMIT trial.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 72-72
Author(s):  
Michiya Kobayashi ◽  
Akira Tsuburaya ◽  
Kazuhiro Yoshida ◽  
Shigefumi Yoshino ◽  
Yumi Miyashita ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adjuvant Chemotherapy ◽  
Safety Data ◽  
Data Monitoring Committee ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Number Of Patients ◽  
Grade 3 ◽  
Lavage Cytology ◽  
Disease Free

72 Background: Adjuvant chemotherapy with fluoropyrimidine (FP) with or without platinum for gastric cancer (GC) has become standard almost worldwide; however, there has been no comparison among concurrent, sequential, and monotherapy. Paclitaxel (PTX) is one of key drugs in GC widely used as 2nd-line chemotherapy in Japan. Methods: SAMIT is a randomized, multicenter phase III study of FP (S1 or UFT) vs. PTX followed by FP in patients (pts) with gastric adenocarcinoma. Eligibility includes T3/T4, N0-2, M0 except for positive lavage cytology, chemotherapy- and radiotherapy- naive, being able to start chemotherapy 14 and 56 days after D2 gastrectomy. Pts received either UFT 267 mg/m2/day for 4w, q4w x 6 cycles (arm A); S1 80 mg/m2/day for 2w, q3w x 8 cycles (arm B); PTX 80 mg/m2 Day 1, 8 for the first 3w x 1 cycle, Day 1, 8, 15 q4w x 2 cycles, followed by UFT 267 mg/m2/day for 4w, q4w x 3 cycles (arm C); or PTX as in C, followed by S1 80 mg/m2/day for 2w, q3w x 4 cycles (arm D). The FP cycles was prolonged by 24w after ACTS-GC publication in 2007. Primary endpoint is disease-free survival and total number of patients was calculated to be1480 where 90% power for superiority of C+D group vs. A+B. The Independent Data Monitoring Committee undertook a review of the 1417 pts at the 2nd interim analysis in 2011. Results: Arm A (n=353), arm B (n=359), arm C (n=352), arm D (n=353) were well balanced for baseline factors. The compliance with UFT in arm A and S1 in B was 74% and 76% in the first 12 weeks, and 89% and 90% between week 37 and 48; that in arm C and D was 83% and 80% in the second 12 weeks, and 94% and 84% between week 37 and 48. Numbers of grade 3/4 hematological and non-hematological adverse events (AEs) were 3 and 46, 0 and 64, 5 and 35, and 16 and 67 for arm A, B, C, and D, respectively. Anorexia was the most common AE observed in 5.8%, 6.8%, 1.7%, and 5.1% for arm A, B, C, and D, respectively. There were 363/1323 (27%) deaths and 762/1323 (58%) of pts survived disease free. Conclusions: Adjuvant chemotherapy with sequential PTX and FP for GC was safe and the compliance of the FP part could be better than that of FP monotherapy. The final efficacy results will be formally assessed in 2012.

scholarly journals Initial Safety Report of NSABP C-08: A Randomized Phase III Study of Modified FOLFOX6 With or Without Bevacizumab for the Adjuvant Treatment of Patients With Stage II or III Colon Cancer

2009 ◽  
Vol 27 (20) ◽  
pp. 3385-3390 ◽  
Author(s):  
Carmen J. Allegra ◽  
Greg Yothers ◽  
Michael J. O'Connell ◽  
Saima Sharif ◽  
Linda H. Colangelo ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Treatment ◽  
Safety Information ◽  
Stage Ii ◽  
Phase Iii ◽  
Wound Complications ◽  
Bowel Project ◽  
Phase Iii Study ◽  
Modified Folfox6 ◽  
Grade 3

Purpose The National Surgical Adjuvant Breast and Bowel Project C-08 trial was designed to investigate the safety and effectiveness of adding bevacizumab to modified infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) 6 regimen for the adjuvant treatment of patients with stage II or III colon cancer. We present safety information in advance of the planned analysis of efficacy. Patients and Methods Among 2,710 randomly assigned patients, demographic factors were balanced. Patients received modified FOLFOX6 every 2 weeks × 12 or modified FOLFOX6 plus bevacizumab (5 mg/kg every 2 weeks × 26, experimental group). Results Overall rates of grade 4 or 5 toxicities were nearly identical in the FOLFOX6 and FOLFOX6 plus bevacizumab arms (15.2% and 15.0%, respectively). Six-month mortality rates were 0.96% and 0.90% for the control and experimental groups, respectively. Grade 3+ toxicities that occurred more often in the experimental arm versus control arm included hypertension (12% v 1.8%, respectively), wound complications (abdominal incisional hernia or infusion port dehiscence/inflammation; 1.7% v 0.3%, respectively), pain (11.1% v 6.3%, respectively), and proteinuria (2.7% v 0.8%, respectively). Grade 2+ neuropathy was increased in the experimental arm versus the control arm (grade 2, 33% v 29%, respectively; grade 3, 16% v 14%, respectively; and grade 4, < 1% each). In the experimental arm versus control arm, significantly less thrombocytopenia (1.4% v 3.4%, respectively) and fewer allergic reactions (3.1% v 4.7%, respectively) were observed. Advanced age was associated with a significantly greater rate of grade 4 and 5 toxicities regardless of treatment. Conclusion Bevacizumab with modified FOLFOX6 is well tolerated in the surgical adjuvant setting in these patients. No significant increase in GI perforation, hemorrhage, arterial or venous thrombotic events, or death with the addition of bevacizumab to modified FOLFOX6 has been observed. Follow-up for potential delayed adverse effects and efficacy is ongoing.

Potential Regional Differences for the Tolerability Profiles of Fluoropyrimidines

2008 ◽  
Vol 26 (13) ◽  
pp. 2118-2123 ◽  
Author(s):  
Daniel G. Haller ◽  
Jim Cassidy ◽  
Stephen J. Clarke ◽  
David Cunningham ◽  
Eric Van Cutsem ◽  
...  
Keyword(s):  
Colon Cancer ◽  
East Asia ◽  
Regional Differences ◽  
East Asian ◽  
Safety Data ◽  
Phase Iii ◽  
Asian Patients ◽  
The World ◽  
Grade 3 ◽  
East Asian Patients

PurposeWe conducted a retrospective analysis of safety data from randomized, single-agent fluoropyrimidine clinical trials (bolus fluorouracil/leucovorin [FU/LV] and capecitabine) to test the hypothesis that there are regional differences in fluoropyrimidine tolerability.MethodsTreatment-related safety data from three phase III clinical studies were analyzed by multivariate analysis: two comparing capecitabine with bolus FU/LV in metastatic colorectal cancer (MCRC) and one comparing capecitabine plus oxaliplatin (XELOX) with bolus FU/LV as adjuvant treatment for colon cancer. The United States (US) was compared with non-US countries (all three studies) and with the rest of the world and East Asia (adjuvant study).ResultsIn the MCRC studies (n = 1,189), more grade 3/4 adverse events (AEs; relative risk [RR], 1.77), dose reductions (RR, 1.72), and discontinuations (RR, 1.83) were reported in US versus non-US patients. Likewise, in the adjuvant colon cancer study (n = 1,864), more grade 3/4 AEs (RR, 1.47) and discontinuations (RR, 2.09) were reported in US versus non-US patients. After further dividing non-US patients into those in East Asia and the rest of the world, differential RRs for related grade 3/4 AEs, grade 4 AEs, and serious AEs were again observed, with East Asian patients having the lowest and US patients the highest RR.ConclusionRegional differences exist in the tolerability profiles of fluoropyrimidines. More treatment-related toxicity was reported in the US compared with the rest of the world for bolus FU/LV and capecitabine in first-line MCRC and adjuvant colon cancer. In the adjuvant setting, a range of fluoropyrimidine tolerability was observed, with East Asian patients having the lowest, and US patients the highest, RR.

scholarly journals Safety data from the phase III Japanese ACHIEVE trial: part of an international, prospective, planned pooled analysis of six phase III trials comparing 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy for stage III colon cancer

ESMO Open ◽  
2018 ◽  
Vol 3 (3) ◽  
pp. e000354 ◽  
Author(s):  
Masahito Kotaka ◽  
Takeharu Yamanaka ◽  
Takayuki Yoshino ◽  
Dai Manaka ◽  
Tetsuya Eto ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Safety Data ◽  
Sensory Neuropathy ◽  
Pooled Analysis ◽  
Phase Iii ◽  
Stage Iii ◽  
Open Label ◽  
Stage Iii Colon Cancer ◽  
Grade 3

BackgroundThe International Duration Evaluation of Adjuvant chemotherapy project investigated whether a shorter duration of oxaliplatin-based adjuvant chemotherapy was as effective as 6 months of identical chemotherapy for resected stage III colon cancer. As part of this project, we report safety data from the Japanese ACHIEVE study (JFMC47-1202-C3).Patients and methodsACHIEVE was an open-label, multicentre trial randomising patients with stage III colon cancer to receive 3 m or 6 m of mFOLFOX6/CAPOX after surgery. Choice of regimen was declared before randomisation by a site investigator.ResultsBetween August 2012 and June 2014, 1313 patients were enrolled and, of those, 1277 were analysed for the safety analysis, with 635 in arm 6 (mFOLFOX6, n=158; CAPOX, n=477) and 642 in arm 3 (mFOLFOX6, n=161; CAPOX, n=481). Grade 3 or worse peripheral sensory neuropathy (PSN) developed in 5%/0.6% of patients receiving mFOLFOX6 in arm 6/3 (p=0.019) and 6%/1% of those receiving CAPOX in arm 6/3 (p<0.001). Similarly, grade 2 or worse PSN developed in 36%/11% of patients receiving mFOLFOX6 in arm 6/3 (p<0.001) and 37%/14% of those receiving CAPOX in arm 6/3 (p<0.001). An association between baseline creatinine clearance (CCr) and adverse events (AEs) was found that patients with CAPOX were significantly more likely to develop AEs ≥grade 3 when they had a CCr ≤50 (OR 1.67; p=0.048).ConclusionsWe confirmed in the Japanese population that the shorter duration of adjuvant chemotherapy resulted in a significant reduction of PSN. In patients with CAPOX, renal function was significantly related to severe AEs.Trial registration numberUMIN000008543, Results.

Final safety findings from a randomized phase III trial of capecitabine + oxaliplatin (XELOX) vs. bolus 5-FU/LV as adjuvant therapy for patients (pts) with stage III colon cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3569-3569 ◽  
Author(s):  
H. J. Schmoll ◽  
J. Tabernero ◽  
M. Nowacki ◽  
J. Maroun ◽  
T. Price ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Therapy ◽  
Safety Data ◽  
Disease Free Survival ◽  
Skin Toxicity ◽  
Phase Iii ◽  
Stage Iii ◽  
Standard Regimen ◽  
Stage Iii Colon Cancer ◽  
Grade 3

3569 Background: Adjuvant capecitabine results in at least equivalent disease-free survival (DFS) to i.v. bolus 5-FU/LV in stage III colon cancer [Twelves et al. 2005]. Early phase III data in 1st-line metastatic colorectal cancer suggest that XELOX is as safe as oxaliplatin + infusional 5-FU ± LV [Sastre et al. 2005; Ducreux et al. 2005]. The XELOXA study compared safety and efficacy of XELOX vs. bolus 5-FU/LV (the standard regimen at study start) as adjuvant therapy for stage III colon cancer. Methods: Pts with resected disease were randomized to receive either XELOX (capecitabine 1000 mg/m2 bid d1–14 + oxaliplatin 130 mg/m2 d1, q3w for 8 cycles) or i.v. bolus 5-FU/LV (Mayo Clinic, LV 20 mg/m2 + 5-FU 425 mg/m2 d1–5, q4w for 6 cycles; or Roswell Park [RP], LV 500 mg/m2 + 5-FU 500 mg/m2 d1, w1–6 in 8w cycles x4). Centers’ preferred 5-FU/LV regimen was selected at study start and used in all pts. Results: 1861/1886 pts randomized between Apr 03 and Oct 04 are evaluable for safety. The rate of related grade 3/4 adverse events (AEs) was 54% for XELOX and 45% for 5-FU/LV ( table ). 60-day all cause mortality was 1.0% in both arms. Treatment-related death rate within 28 days from last dose was 0.7% for XELOX and 0.5% for 5-FU/LV. Conclusions: XELOX causes less myelosuppression and stomatitis but more skin toxicity than 5-FU/LV. The inclusion of oxaliplatin adds neurosensory toxicity. Cross-study comparison of grade 3/4 AEs in the current and MOSAIC trials suggests that XELOX safety is similar to FOLFOX4, with the advantage of an oral fluoropyrimidine-based regimen. Final safety data will be presented at the meeting, and efficacy data will be available in 2007. [Table: see text] [Table: see text]

scholarly journals COVID-19 Vaccine Safety in Cancer Patients: A Single Centre Experience

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3573
Author(s):  
Alfred Chung Pui So ◽  
Harriet McGrath ◽  
Jonathan Ting ◽  
Krishnie Srikandarajah ◽  
Styliani Germanou ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Safety Data ◽  
Vaccine Safety ◽  
Phase Iii ◽  
Solid Malignancy ◽  
Common Grade ◽  
Phase Iii Trials ◽  
Oncology Care ◽  
Grade 3 ◽  
Oncology Centre

Emergency approval of vaccines against COVID-19 provides an opportunity for us to return to pre-pandemic oncology care. However, safety data in cancer patients is lacking due to their exclusion from most phase III trials. We included all patients aged less than 65 years who received a COVID-19 vaccine from 8 December 2020 to 28 February 2021 at our London tertiary oncology centre. Solicited and unsolicited vaccine-related adverse events (VRAEs) were collected using telephone or face-to-face consultation. Within the study period, 373 patients received their first dose of vaccine: Pfizer/BioNTech (75.1%), Oxford/AstraZeneca (23.6%), Moderna (0.3%), and unknown (1.1%). Median follow-up was 25 days (5–85). Median age was 56 years (19–65). Of the patients, 94.9% had a solid malignancy and 76.7% were stage 3–4. The most common cancers were breast (34.0%), lung (13.4%), colorectal (10.2%), and gynaecological (10.2%). Of the patients, 88.5% were receiving anti-cancer treatment (36.2% parenteral chemotherapy and 15.3% immunotherapy), 76.1% developed any grade VRAE of which 2.1% were grade 3. No grade 4/5 or anaphylaxis were observed. The most common VRAEs within 7 days post-vaccination were sore arm (61.7%), fatigue (18.2%), and headaches (12.1%). Most common grade 3 VRAE was fatigue (1.1%). Our results demonstrate that COVID-19 vaccines in oncology patients have mild reactogenicity.

scholarly journals Systemic therapy for colorectal cancer

2003 ◽  
Vol 11 (4) ◽  
pp. 255-263 ◽  
Author(s):  
Borut Stabuc
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Metastatic Colorectal Cancer ◽  
Adjuvant Treatment ◽  
Randomized Clinical Trials ◽  
Response Rate ◽  
Phase Iii ◽  
Oral Fluoropyrimidines ◽  
Significant Difference

Colorectal cancer alone accounts for around 200,000 deaths in Europe and represents a significant health problem. Although about fifty percent of patients are cured by surgery alone, the other half will eventually die due to metastatic disease, which includes approximately 25% of patients who have evidence of metastases at the time of diagnosis. Surgical resection of the primary tumor and regional lymph nodes is the only curative therapy for colorectal cancer. However, adjuvant chemotherapy in stage III for colon cancer following curative resection has been shown to reduce the risk of recurrence by 19-40% and of death by 16-33%. Today, 5-fluoroUracil and Leucovorin given for six months may represent the best adjuvant treatment available The contribution of levamisole to adjuvant treatment seems to be marginal, if any. The benefit of adjuvant chemotherapy for the patients with Dukes B colon cancer is less clear. A meta-analysis of 1,381 patients with advanced colorectal cancer showed a significant increase in response rate with the bolus 5-fluoroUracil and Leucovorin versus 5-fluoroUracil alone but no significant difference in median survival. Continuous infusion allows higher doses of 5-FU than rapid bolus infusion and improves response rate survival and time to progression. Oral fluoropyrimidines (capecitabine and Uracil/Tegafur [UFT]) are as active as intravenous fluoropyrimidines. Compared to intravenous 5FU, oral fluoropyrimidines have safety advantages clinical benefits, and are more convenient for patients. Phase III randomized clinical trials in patients with metastatic colorectal cancer demonstrate the significant superiority of combining irinotecan with 5-fluoroUracil and Leucovorin or oxaliplatin with 5-fluoroUracil and Leucovorin over the same 5-fluoroUracil and Leucovorin alone. Several phase II studies have shown that the combination of the oral fluoropyrimidines plus irinotecan or oxaliplatin is very active in metastatic colorectal cancer. Trials with agents acting on novel targets in colorectal cancer are progressing rapidly, including doxifluridine, new inhibitors of thymidylate synthase (ZD9331), oral camptothecins (Rubitecan), multitarget antifolate antimetabolite (Premetrexet), inhibitors of epidermal growth factor receptor (Cetuximab), COX-2 inhibitors (celecoxib) and farnesyltransferaze inhibitors (Zarnestra). However, a few randomized trials failed to show a survival advantage compared with placebo in patients with advanced refractory colorectal cancer.

scholarly journals Bevacizumab as adjuvant treatment for colon cancer: Updated results from the AVANT phase III study by the GERCOR group

2019 ◽  
Vol 30 ◽  
pp. v211
Author(s):  
T. André ◽  
D. Vernerey ◽  
S.-A. Im ◽  
G.M. Bodoky ◽  
R. Buzzoni ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Treatment ◽  
Phase Iii ◽  
Phase Iii Study

scholarly journals Adjuvant Capecitabine With Docetaxel and Cyclophosphamide Plus Epirubicin for Triple-Negative Breast Cancer (CBCSG010): An Open-Label, Randomized, Multicenter, Phase III Trial

2020 ◽  
Vol 38 (16) ◽  
pp. 1774-1784 ◽  
Author(s):  
Junjie Li ◽  
Keda Yu ◽  
Da Pang ◽  
Changqin Wang ◽  
Jun Jiang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Safety Data ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Control Treatment ◽  
Open Label ◽  
Phase Iii Trial ◽  
Grade 3

PURPOSE Standard adjuvant chemotherapy for triple-negative breast cancer (TNBC) includes a taxane and an anthracycline. Concomitant capecitabine may be beneficial, but robust data to support this are lacking. The efficacy and safety of the addition of capecitabine into the TNBC adjuvant treatment regimen was evaluated. PATIENTS AND METHODS This randomized, open-label, phase III trial was conducted in China. Eligible female patients with early TNBC after definitive surgery were randomly assigned (1:1) to either capecitabine (3 cycles of capecitabine and docetaxel followed by 3 cycles of capecitabine, epirubicin, and cyclophosphamide) or control treatment (3 cycles of docetaxel followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide). Randomization was centralized without stratification. The primary end point was disease-free survival (DFS). RESULTS Between June 2012 and December 2013, 636 patients with TNBC were screened, and 585 were randomly assigned to treatment (control, 288; capecitabine, 297). Median follow-up was 67 months. The 5-year DFS rate was higher for capecitabine than for control treatment (86.3% v 80.4%; hazard ratio, 0.66; 95% CI, 0.44 to 0.99; P = .044). Five-year overall survival rates were numerically higher but not significantly improved (capecitabine, 93.3%; control, 90.7%). Overall, 39.1% of patients had capecitabine dose reductions, and 8.4% reported grade ≥ 3 hand-foot syndrome. The most common grade ≥ 3 hematologic toxicities were neutropenia (capecitabine, 136 [45.8%]; control, 118 [41.0%]) and febrile neutropenia (capecitabine, 50 [16.8%]; control, 46 [16.0%]). Safety data were similar to the known capecitabine safety profile and generally comparable between arms. CONCLUSION Capecitabine when added to 3 cycles of docetaxel followed by 3 cycles of a 3-drug anthracycline combination containing capecitabine instead of fluorouracil significantly improved DFS in TNBC without new safety concerns.

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