Efficacy and Long-term Peripheral Sensory Neuropathy of 3 vs 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Colon Cancer

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.

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JOIN trial: treatment outcome and recovery status of peripheral sensory neuropathy during a 3-year follow-up in patients receiving modified FOLFOX6 as adjuvant treatment for stage II/III colon cancer

Cancer Chemotherapy and Pharmacology ◽

10.1007/s00280-019-03957-5 ◽

2019 ◽

Vol 84 (6) ◽

pp. 1269-1277

Author(s):

Takayuki Yoshino ◽

Masahito Kotaka ◽

Katsunori Shinozaki ◽

Tetsuo Touyama ◽

Dai Manaka ◽

...

Keyword(s):

Colon Cancer ◽

Disease Free Survival ◽

Sensory Neuropathy ◽

Stage Ii ◽

Peripheral Sensory Neuropathy ◽

Free Survival ◽

Modified Folfox6 ◽

Recovery Status ◽

Peripheral Sensory

Abstract Purpose Adjuvant FOLFOX therapy is an established standard-of-care for resected colon cancer. Peripheral sensory neuropathy (PSN) is regarded as the major toxicity issue related to FOLFOX therapy. There have been a few reports on the recovery status from PSN thereafter. JOIN trial investigated the tolerability and efficacy of adjuvant modified FOLFOX6 (mFOLFOX6) in Japanese patients with stage II/III colon cancer. Methods Twelve cycles of mFOLFOX6 were given to patients with stage II/III curatively resected colon cancer. Treatment outcomes, including disease-free survival (DFS), relapse-free survival (RFS), overall survival (OS), and recovery status of PSN during 3-year follow-up, were investigated. Results Of the 882 patients enrolled from 2010 to 2012, 864 were eligible for the efficacy analyses. Three-year DFS, RFS, and OS were favorable in 92.1, 92.8, and 97.4% of stage II patients; 76.4, 77.9, and 93.8% of stage IIIA/B; and 61.6, 62.7, and 85.9% of stage IIIC, respectively. The cumulative incidence of PSN during treatment was 47.8% in grade 1 (G1), 30.3% in G2, and 5.8% in G3. For those with G3 PSN during treatment, there was gradual recovery in 1.1% of patients at 12 months after enrollment, 0.5% at 24 months, and 0.2% at 36 months. However, G1 or G2 residual PSN after 3 years was observed in 21.0% (18.7%, G1; 2.3%, G2). Conclusions Adjuvant mFOLFOX6 therapy was effective and well tolerated in patients with stage II/III colon cancer. Most patients recovered from G3 PSN related to oxaliplatin, but approximately 20% of patients had G1 or G2 PSN at 3-year follow-up.

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Treatment outcome and recovery from peripheral sensory neuropathy during a 3-year follow-up in patients receiving modified FOLFOX6 as adjuvant treatment for stage II/III colon cancer (JFMC41-1001-C2: JOIN Trial).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.703 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 703-703 ◽

Cited By ~ 1

Author(s):

Dai Manaka ◽

Masahito Kotaka ◽

Katsunori Shinozaki ◽

Tetsuo Touyama ◽

Takanori Matsui ◽

...

Keyword(s):

Colon Cancer ◽

Treatment Outcome ◽

Lymph Nodes ◽

Sensory Neuropathy ◽

Stage Ii ◽

Peripheral Sensory Neuropathy ◽

Free Survival ◽

Modified Folfox6 ◽

Peripheral Sensory

703 Background: The JOIN Trial investigated safety and efficacy of modified FOLFOX6 (mFOLFOX6) in Japanese patients (pts) with stage II/III colon cancer. In the initial safety report, incidence of ≥ grade 3 (G3) peripheral sensory neuropathy (PSN) was 5.8% during treatment. Methods: Twelve cycles of mFOLFOX6 were given to pts with the following criteria: stage II/III curatively resected colon cancer; ECOG Performance Status (PS) of 0–1; age, ≥ 20 years; and adequate organ function. We report the treatment outcome results, including disease-free survival (DFS), relapse-free survival (RFS), overall survival (OS), and recovery from PSN during 3-year follow-up. Results: From November 2010 to March 2012, 882 pts were enrolled. In the efficacy group (N = 864; median follow-up, 3 years), pt characteristics were as follows: median age, 64 years; male, 53.8%; PS 0, 93.8%; stage II/IIIA/IIIB/IIIC (TNM), 18.5/7.3/52.5/21.6%; and lymph nodes examined, < 12/ > 12/unknown: 17.2/82.5/0.2%, respectively. Three-year DFS, RFS, and OS were 76.1, 77.3, and 92.7%, respectively. Favorable 3-year DFS, RFS, and OS were 92.1, 92.8, and 97.4% in stage II patients; 76.4, 77.9, and 93.8% in stage IIIA/B; and 61.6, 62.7, and 85.9% in stage IIIC, respectively. The main recurrent sites were liver (7.6%), lung (7.3%), and lymph nodes (5.2%). In multivariate Cox regression analysis, tumor histology, venous invasion, and lymph node metastatic ratio were statistically significant prognostic factors for DFS, RFS, and OS. Cumulative incidence of PSN during treatment was 47.8% in G1, 30.3% in G2, and 5.8% in G3. For those with G3 PSN during treatment, there was gradual recovery in 1.1% at 12 months after enrollment, 0.5% at 24 months, and 0.2% at 36 months. However, G1 and G2 residual PSN after 3 years was observed in 21.0% of pts (18.7%, G1; 2.3%, G2). Conclusions: Efficacy and safety of adjuvant mFOLFOX6 in pts with stage II/III colon cancer can be confirmed. Most pts successfully recovered from G3 PSN related to oxaliplatin, but G1 and G2 PSN was irreversible in one-fifth of pts at the 3-year follow-up. Clinical trial information: UMIN000004443.

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Four versus six chemotherapy cycles in endometrial carcinoma with a high risk of recurrence: a retrospective study

Japanese Journal of Clinical Oncology ◽

10.1093/jjco/hyaa047 ◽

2020 ◽

Vol 50 (8) ◽

pp. 882-888 ◽

Cited By ~ 1

Author(s):

Michinori Mayama ◽

Hiroshi Asano ◽

Eiji Nomura ◽

Kei Ihira ◽

Ayako Nozaki ◽

...

Keyword(s):

Endometrial Cancer ◽

High Risk ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Sensory Neuropathy ◽

Survival Outcomes ◽

Peripheral Sensory Neuropathy ◽

Risk Of Recurrence ◽

Peripheral Sensory ◽

Disease Free

Abstract Objective This study compared the survival outcomes and the incidence of chemotherapy-related adverse events in endometrial cancer patients who received four and six cycles of adjuvant chemotherapy to examine the optimal number of adjuvant chemotherapy cycles. Methods A total of 112 patients with endometrial cancer with a high risk of recurrence were retrospectively enrolled; 46 patients received four cycles and 66 received six cycles of adjuvant chemotherapy. Between-group differences of overall survival, disease-free survival, hematological and non-hematological toxicities were analyzed. Baseline patient’s background differences were assessed with inverse probability of treatment weighting using propensity score. Results Overall and disease-free survivals between the two groups were not significantly different. Paclitaxel + carboplatin, every 3–4 weeks was the most frequently used chemotherapy regimen in both groups. Patients in the six-cycle chemotherapy group developed neutropenia G4 or febrile neutropenia more frequently than those in the four-cycle group; odds ratio (95% confidence interval) is 4.07 (1.51–10.96). Peripheral sensory neuropathy was the most frequently observed non-hematological toxicity; the incidence of peripheral sensory neuropathy was not significantly different between four- and six-cycle chemotherapy group, P = 0.832. The result was same in the subgroup analysis in patients who received TC regimen, P = 0.455. Conclusion This study implies a possible benefit of fewer cycles of adjuvant chemotherapy in endometrial cancer patients with a high risk of recurrence because of the lower incidence of hematological toxicities without impairing survival outcomes.

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