Mecobalamin as a Neuroprotective Effector against Oxaliplatin-Based Chemotherapy in Colon and Rectal Cancer Patients

Care Weekly ◽  
2021 ◽  
pp. 1-5
Author(s):  
Li Hongyan ◽  
Lu Wanting ◽  
Li Fei
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Sensory Neuropathy ◽  
Control Group ◽  
Placebo Control ◽  
Case Group ◽  
Colon And Rectal Cancer ◽  
Grade 3

Palliative chemotherapy prolongs survival and improves quality of life. However, a variety of chemotherapeutics including oxaliplatin can cause severe side effects during treatments, leading to painful symptoms that might result in the interruption of cancer treatment. Although adding oxaliplatin to fluorouracil and leucovorin in adjuvant chemotherapy for colon and rectal cancer may improve disease-free survival, it also increases grade 3–4 sensory neuropathy. Our study aimed to determine whether oral Mecobalamin is neuroprotective against oxaliplatin-induced neuropathy. Forty-six stage III colon and rectal cancer patients receiving adjuvant biweekly oxaliplatin were randomized to oral Mecobalamin (1,500 mg; case group) or placebo (control group). Clinical neurological and electrophysiological evaluations were performed at baseline and after 4, 8, and 12 treatment cycles. Treatment-related toxicity was evaluated based on National Cancer Institute (NCI) criteria. After four cycles of chemotherapy, 9 of 23 patients in the control group and 8 of 23 patients in case group experienced grade 1 sensory neuropathy. After eight cycles, 13 patients experienced sensory neuropathy (grade 2–4 toxicity) in the control group; however, no patients in the case group experienced sensory neuropathy (P < 0.05). After 12 cycles, grade 2–4 sensory neuropathy was observed in 20 patients in the control group, but only in 4 patients in the case group (P < 0.05). We did not observe any significant electrophysiological changes in the case group after 4, 8, or 12 cycles of chemotherapy. Thus, we demonstrated that oral Mecobalamin reduces the incidence of neuropathy in colon and rectal cancer patients receiving oxaliplatin-based adjuvant chemotherapy.

scholarly journals Phase II study of an oxaliplatin-based regimen for relapsed colon cancer patients treated with oxaliplatin-based adjuvant chemotherapy (INSPIRE study)

2021 ◽  
Author(s):  
Keiichiro Ishibashi ◽  
Toru Aoyama ◽  
Masahito Kotaka ◽  
Hironaga Satake ◽  
Yasushi Tsuji ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
First Line ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Peripheral Sensory ◽  
Line Chemotherapy

Abstract Background The aim of this study was to evaluate the efficacy and safety of first-line chemotherapy with re-introduction of oxaliplatin (OX) more than 6 months after adjuvant chemotherapy including OX. Methods Stage II/III colon cancer patients with neuropathies of grade ≤ 1 who relapsed more than 6 months after adjuvant chemotherapy including OX were considered eligible. Eligible patients were treated with 5-fluorouracil, l-leucovorin and OX plus molecularly targeted agents or capecitabine and OX plus bevacizumab (BV) or S-1 and OX plus BV. The primary endpoint was the progression-free survival (PFS), and the secondary endpoints were the overall survival (OS), response rate (RR) and toxicity. Results A total of 50 patients were enrolled between September 2013 and May 2019. Twelve patients received 5-fluorouracil, l-leucovorin and OX (FOLFOX) plus BV, 21 patients received capecitabine and OX plus BV, 10 patients received S-1 and OX plus BV and 7 patients received FOLFOX plus cetuximab or panitumumab. The median PFS was 11.5 months (95% confidence interval [CI] 8.3–16.0), the median OS was 45.4 months (95% CI 37.4–NA), and the RR was 56.0% (95% CI 42.3–68.8). Adverse events of grade ≥ 3 that occurred in ≥ 5% of cases were neutropenia in 6 patients (12%), peripheral sensory neuropathy in 5 patients (10%), diarrhea in 4 patients (8%), hypertension in 4 patients (8%), anorexia in 3 patients (6%) and allergic reactions in 3 patients (6%). Conclusions First-line chemotherapy with re-introduction of OX more than 6 months after adjuvant chemotherapy including OX can be used safely with expected efficacy for relapsed colon cancer patients.

Evaluation of the re-introducing FOLFOX or XELOX ± bevacizumab in relapsed colorectal cancer patients treated with oxaliplatin as adjuvant chemotherapy (REACT study).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 634-634
Author(s):  
Shigeyoshi Iwamoto ◽  
Masahito Kotaka ◽  
Taro Ikumoto ◽  
Daisuke Sakai ◽  
Toshihiro Kudo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Past History ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Common Grade ◽  
Grade 3 ◽  
Colorectal Cancer Patients ◽  
React Study

634 Background: Chemotherapy in relapsed colon cancer patients (pts) treated with oxaliplatin as adjuvant chemotherapy is under debate. REACT study aimed to investigate the efficacy of re-introducing FOLFOX or XELOX ± bevacizumab therapy for recurrent colorectal cancer pts after adjuvant chemotherapy including oxaliplatin. Methods: Pts with past history of adjuvant chemotherapy including oxaliplatin (FOLFOX, XELOX or SOX) with a cumulative dose of more than 400 mg/m2, and recurrence observed by imaging after more than 6 months post adjuvant chemotherapy participated in this trial. Primary endpoints were response rate (RR) and disease control rate (DCR). Key secondary endpoints were progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS) and safety. Results: A total of 31 pts were enrolled between Oct 2012 and Oct 2016. Of 29 eligible pts, 7 received FOLFOX ± bevacizumab, and 22 received XELOX ± bevacizumab. 28 of the pts received bevacizumab. The RR was 66.7% (95% CI, 46.0-83.5) and the DCR was 88.9% (95% CI, 70.8-97.6). The RR for oxaliplatin free-interval was 100.0% (n = 4, 95% CI, 39.8-100.0) in 6 to 12 months, 60.9% (n = 25, 95% CI, 38.5-80.3%) over 12 month, respectively. Median PFS, TTF and OS were 10.9 months (95% CI, 7.0-19.0), 6.3 months (95% CI, 2.8-8.0) and 29.1 months (95% CI, 20.3-53.3). The most common grade 3 or 4 adverse event was hypertension (19.4%). Grade 3 or worse peripheral sensory neuropathy developed only two pts (6.5%). Allergic reactions occurred in 12.9% of the pts, with one (3.2%) grade 3 episode. There were no other severe treatment-related adverse events. Conclusions: Re-introduction of oxaliplatin was feasible and achieved high RR or DCR in after more than 6 months post adjuvant chemotherapy including oxaliplatin. Clinical trial information: UMIN000006523.

Phase II trial of adjuvant mFOLFOX6 after metastasectomy for pulmonary metastasis of colorectal cancer: WJOG5810G.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4097-4097
Author(s):  
Nozomu Machida ◽  
Takehiro Okumura ◽  
Junji Kishimoto ◽  
Narikazu Boku ◽  
Tomohiro Nishina ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Pulmonary Metastasis ◽  
Disease Free Survival ◽  
Sensory Neuropathy ◽  
Eligibility Criteria ◽  
Phase 2 Trial ◽  
Grade 3 ◽  
Ecog Ps ◽  
Peripheral Sensory

4097 Background: Resection of pulmonary metastasis (PM) is widely accepted to improve the prognosis in selected patients (pts) with metastatic colorectal cancer (CRC). However, the clinical implication of adjuvant chemotherapy after metastasectomy of PM is unknown. We conducted a multi-center phase 2 trial of adjuvant chemotherapy with mFOLFOX6 after metastasectomy of PM-CRC. Methods: Main eligibility criteria were first curative metastasectomy of 4 or less PMs and no prior chemotherapy except for adjuvant chemotherapy with fluoropyrimidine monotherapy after curative resection of primary or extrathoracic CRC metastasis. The study treatment was 12 courses of mFOLFOX6 (oxaliplatin 85 mg/m2, l-leucovorin 200 mg/m2, 5-fluorouracil 400 mg/m2 bolus followed by 2400 mg/m2 continuous infusion, every 2 w). The primary endpoint was overall survival (OS). The secondary endpoints included disease-free survival (DFS), adverse events (AEs), and recurrence sites. The sample size was determined to be 93 expecting 5-year OS rate of 50% with threshold 35% (90% power, alpha error 5%). Results: Fifty-two pts from 34 institutions were enrolled between July 2011 and July 2014. Patient enrollment was closed prematurely because of slow accrual. Four patients were ineligible after enrollment and the safety and efficacy cohort comprised 52 and 48 patients, respectively. Patient backgrounds were as follows: gender (male/female) 31/21, median age (range) 63 (42-75) years, ECOG PS (0/1) 48/4, primary site (colon/rectum) 18/34, number of PM (1/2/3/4) 36/9/5/2, synchronous/metachronous PM 11/41, and unilateral/bilateral PM 40/12. With the median follow-up time of 6.0 (1.8-7.7) years, 5-year OS rate was 86% (95% CI: 72-93) and 5-year DFS rate was 59% (95% CI: 43-71). Tumors recurred in 19 patients (13 lung, 3 liver and 7 others). Total 41 pts (79%) completed 12 courses of mFOLFOX6 (reasons for discontinuation: AEs in 3, refusal due to AEs in 8). AEs ( > Grade 3) were neutropenia 50%, fatigue 8%, peripheral sensory neuropathy 8%, appetite loss 4%, diarrhea 4%, febrile neutropenia 2% and allergic reaction 2%. There was no treatment related death. Conclusions: Adjuvant mFOLFOX6 is feasible and may be effective after metastasectomy for PM-CRC, considering much better OS than we had expected. Clinical trial information: UMIN000005693 .

scholarly journals Myosteatosis Differentially Affects the Prognosis of Non-Metastatic Colon and Rectal Cancer Patients: An Exploratory Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Lara Pozzuto ◽  
Marina Nogueira Silveira ◽  
Maria Carolina Santos Mendes ◽  
Lígia Traldi Macedo ◽  
Felipe Osório Costa ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Rectal Cancer ◽  
Overall Survival ◽  
Body Composition ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Secondary Outcome ◽  
Muscle Area ◽  
Colon And Rectal Cancer ◽  
Skeletal Muscle Area

Body composition performed by computed tomography (CT) impacts on cancer patients’ prognoses and responses to treatment. Myosteatosis has been related to overall survival (OS) and disease-specific survival in colorectal cancer (CRC); however, the independent impact of the association of myosteatosis with prognosis in colon cancer (CC) and rectal cancer (RC) is still unclear. CT was performed at the L3 level to assess body composition features in 227 patients with CRC. Clinical parameters were collected. Overall survival (OS) was the primary outcome, and the secondary outcome was disease-free survival (DFS). Skeletal muscle attenuation and intramuscular adipose tissue area were associated with DFS (p = 0.003 and p = 0.011, respectively) and OS (p &lt; 0.001 and p &lt; 0.001, respectively) in CC patients but not in RC patients. Only the skeletal muscle area was associated with better prognosis related to OS in RC patients (p = 0.009). When CC and RC were analyzed separately, myosteatosis influenced survival negatively in CC patients, worsening DFS survival (hazard ratio [HR], 2.70; 95% confidence interval [CI], 1.07–6.82; p = 0.035) and OS (HR, 5.76; 95% CI, 1.31–25.40; p = 0.021). By contrast, the presence of myosteatosis did not influence DFS (HR, 1.02; 95% CI, 0.52–2.03; p = 0.944) or OS (HR, 0.76; 95% CI, 0.33–1.77; p = 0.529) in RC patients. Our study revealed the interference of myosteatosis in the therapy and survival of patients with CC but not in those with RC, strengthening the value of grouping the two types of cancer in body composition analyses.

scholarly journals Danggui Buxue Decoction, a Classical Formula of Traditional Chinese Medicine, Fails to Prevent Myelosuppression in Breast Cancer Patients Treated With Adjuvant Chemotherapy: A Prospective Study

2016 ◽  
Vol 16 (3) ◽  
pp. 406-413 ◽  
Author(s):  
Jin Hong ◽  
Xiaosong Chen ◽  
Jiahui Huang ◽  
Chunqing Li ◽  
Li Zhong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Chinese Medicine ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Control Group ◽  
Breast Cancer Patients ◽  
Classical Formula ◽  
Grade 3 ◽  
Danggui Buxue Decoction ◽  
And Control

Danggui Buxue Decoction (DBD), a classical formula of traditional Chinese medicine (TCM), has an impact on promoting hematopoiesis. The aim of our study was to determine whether DBD can prevent myelosuppression in breast cancer patients treated with adjuvant chemotherapy. We conducted a phase II randomized prospective controlled clinical study. From December 2013 to February 2015, 106 patients were enrolled and randomly assigned (1:1) to the TCM group and control group. The primary end point was incidence of grade 3-4 neutropenia. The secondary end points included incidence of grade 3-4 neutropenia in each cycle, incidence of anemia, and incidence of thrombopenia during 4 cycles. Seventeen patients withdrew from this study, and 89 patients were included in the final analysis. Incidences of grade 3-4 neutropenia during 4 cycles were 57.1% in the TCM group and 59.6% in the control group, and there was no significant difference ( P = .816). Similarly, no significant differences were observed between the 2 groups for incidence of grade 3-4 neutropenia in each cycle. While incidences of anemia were 54.8% and 66.6% for the TCM group and control group, respectively ( P = .280), incidences of thrombopenia were 11.9% for the TCM group and 4.3% for the control group ( P = .248). No significant differences were observed for the incidence of other nonhematological toxicities between the 2 groups. DBD failed to prevent myelosuppression in breast cancer patients treated with adjuvant chemotherapy. Further studies are warranted to validate the efficacy of DBD in selected patients.

Completion and toxicity rates of adjuvant chemotherapy in rectal cancer patients previously treated with neoadjuvant therapy and resection.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 609-609
Author(s):  
C. R. Oxner ◽  
S. Choi ◽  
M. J. Hein ◽  
D. Lim ◽  
S. Shibata ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Karnofsky Performance Scale ◽  
Complication Rates ◽  
Significant Difference ◽  
Previously Treated

609 Background: Adjuvant chemotherapy is recommended after rectal cancer surgery. Yet the success and complication rates of this adjuvant treatment are poorly studied. The purpose of this study is to determine the success rate and define the toxicity profile of adjuvant chemotherapy in rectal cancer patients previously treated with neoadjuvant chemotherapy. Methods: Study design is a retrospective review of patients from December 2002-December 2007 from the City of Hope database. Data is available with 66 patients diagnosed with locally advanced rectal cancer treated with neoadjuvant chemo radiation and resection. Data points analyzed included demographics, chemotherapy-related toxicity and survival. Results: Adjuvant chemotherapy was started in 35/66 (53%) of patients. In 31 cases chemotherapy was not given because of patient refusal or physician preference. 9 patients were lost to follow-up. Follow-up ranged from 9-59 months with median follow-up of 27 months. In the 26 patients with adequate follow up there were a total of 165 episodes of toxic events 3a grade 1. Most of the events were mild to moderate grade 1-2. In 10 patients (28%) 22 major toxicities 3a grade 3 episodes were observed. The median Karnofsky performance scale (KPS) showed no significant difference in patients before and after adjuvant chemotherapy (p = 0.071). The rates of 1-year, 3-year and 5-year survival were 100%, 90%, and 60%, respectively; corresponding disease-free survival was 88%, 83%, and 69% respectively. Conclusions: These preliminary data suggest that only a fraction of rectal cancer patients previously treated with neoadjuvant CRT complete a full course of adjuvant chemotherapy. Future studies will help confirm these preliminary findings and generate an outcome comparison between patients receiving and not receiving adjuvant therapy. No significant financial relationships to disclose.

Adjuvant chemotherapy with oxaliplatin/5-fluorouracil/leucovorin (FOLFOX) versus 5-fluorouracil/leucovorin (FL) in patients with locally advanced rectal cancer after preoperative chemoradiotherapy followed by surgery: A randomized phase II study (The ADORE).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3570-3570 ◽  
Author(s):  
Yong Sang Hong ◽  
Byung-Ho Nam ◽  
Kyung Hae Jung ◽  
Jae-Lyun Lee ◽  
Kyu-Pyo Kim ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Sensory Neuropathy ◽  
Advanced Rectal Cancer ◽  
Preoperative Chemoradiotherapy ◽  
Locally Advanced Rectal Cancer

3570 Background: Preoperative chemoradiotherapy (Pre-CRT) with fluoropyrimidines (Fp) followed by surgery is one of the standard treatments for patients (pts) with locally advanced rectal cancer (LARC); however, the role of adjuvant chemotherapy is still controversial. The aim of this study is to investigate the efficacy of adjuvant FOLFOX for LARC pts who underwent Fp-based Pre-CRT and complete total mesorectal excision (TME). Methods: This randomised phase II study accrued LARC pts whose ypStage was II (ypT3-4/ypN0) or III (any ypT/ypN1-2) after Fp-based Pre-CRT followed by TME. Pts were randomly assigned (1:1) to receive adjuvant chemotherapy either with FL (5-FU 380 mg/m2, leucovorin 20 mg/m2 on D1-5 q 4 weeks X 4 cycles) or FOLFOX (oxaliplatin 85 mg/m2, leucovorin 200 mg/m2 on D1, 5-FU bolus 400 mg/m2 on D1, 5-FU infusion 2400 mg/m2 for 46 hours q 2 weeks X 8 cycles). The primary endpoint was disease-free survival (DFS). Results: A total of 320 pts were randomly assigned (161 FL and 159 FOLFOX) between November 2008 and June 2012, the arms were balanced. By intent-to-treat analysis, estimated 2-year DFS rate was 82.0% in FOLFOX arm and 69.4% in FL arm (HR 0.46 [95% CI, 0.28-0.76], p=0.002) after the median follow-up duration of 22.5 months. The statistical improvements of DFS were maintained regardless of ypStage: 2-year DFS rate was 89.7% (FOLFOX) vs 76.4% (FL) in pts (n=122) with ypStage II (HR 0.32 [0.10-0.98], p=0.035), and 78.1% (FOLFOX) vs 64.4% (FL) in pts (n=198) with ypStage III (HR 0.49, [0.27-0.86], p=0.011). All grade leucopenia (32% vs 22%), neutropenia (70% vs 46%), thrombocytopenia (26% vs 2%) and sensory neuropathy (71% vs5%) were more frequently observed in FOLFOX arm; however, grade 3/4 adverse events (AE) were not different between arms. Conclusions: Adjuvant FOLFOX improved 2-year DFS relative to FL for LARC pts whose ypStage II or III after Fp-based Pre-CRT followed by TME. Significant AEs were not different between arms. The DFS results will be updated in the presentation. Clinical trial information: NCT00807911.

scholarly journals Particle Beam Therapy Tolerance and Outcome on Patients with Autoimmune Diseases: A Single Institution Matched Case–Control Study

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5183
Author(s):  
Giulia Riva ◽  
Barbara Vischioni ◽  
Sara Gandini ◽  
Stefano Cavalieri ◽  
Sara Ronchi ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Particle Beam ◽  
Particle Therapy ◽  
Control Group ◽  
Cancer Type ◽  
Organ Specific ◽  
Radiation Induced ◽  
Grade 3

It is unclear whether autoimmune diseases (ADs) may predispose patients to higher radiation-induced toxicity, and no data are available regarding particle therapy. Our objective was to determine if cancer patients with ADs have a higher incidence of complications after protons (PT) or carbon ion (CIRT) therapy. METHODS. In our retrospective monocentric study, 38 patients with ADs over 1829 patients were treated with particle therapy between 2011 and 2020. Thirteen patients had collagen vascular disease (CVD), five an inflammatory bowel disease (IBD) and twenty patients an organ-specific AD. Each patient was matched with two control patients without ADs on the basis of type/site of cancer, type of particle treatment, age, sex, hypertension and/or diabetes and previous surgery. RESULTS. No G4–5 complications were reported. In the AD group, the frequency of acute grade 3 (G3) toxicity was higher than in the control group (15.8% vs. 2.6%, p = 0.016). Compared to their matched controls, CVD–IBD patients had a higher frequency of G3 acute complications (27.7 vs. 2.6%, p = 0.002). There was no difference between AD patients (7.9%) and controls (2.6%) experiencing late G3 toxicity (p = 0.33). The 2 years disease-free survival was lower in AD patients than in controls (74% vs. 91%, p = 0.01), although the differences in terms of survival were not significant. CONCLUSIONS. G3 acute toxicity was more frequently reported in AD patients after PT or CIRT. Since no severe G4–G5 events were reported and in consideration of the benefit of particle therapy for selected cancers, we conclude that particle therapy should be not discouraged for patients with ADs. Further prospective studies are warranted to gain insight into toxicity in cancer patients with ADs enrolled for particle therapy.

Utility of EUS to identify the effective responders from rectal cancer patients who receive neo-adjuvant chemotherapy

Endoscopy ◽  
2011 ◽  
Vol 43 (S 03) ◽  
Author(s):  
Zhang Xiaoyin ◽  
Guo Xuegang ◽  
Wang Xin ◽  
Du Jianjun ◽  
Zhao Qingchuan ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Neo Adjuvant Chemotherapy
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