Efficacy and tolerability of oxycodone for oxaliplatin-induced peripheral neuropathy and the extension of folfox therapy in colorectal cancer patients.

196 Background: The oxaliplatin-based regimen FOLFOX is widely used to treat patients with advanced colorectal cancer (CRC). However, dose-limiting toxicity after continuous oxaliplatin administration can lead to peripheral neuropathy. Several agents, including opioids, that have been employed to treat oxaliplatin-induced peripheral neuropathy (OIPN) have been examined in clinical settings regarding their protective and therapeutic effects. However, the pharmacotherapy of these agents has not yet been established. Therefore, we investigated the efficacy and tolerability of oxycodone for OIPN and subsequently with FOLFOX therapy in CRC patients. Methods: This was a single-center retrospective study of 64 CRC patients who underwent FOLFOX therapy at the Toho University Sakura Medical Center (Sakura, Japan). Controlled-release (CR) oxycodone was concomitantly administered to 29 patients (OXY group), whereas the additional 35 patients (non-OXY group) were not given oxycodone during the FOLFOX treatment course. The incidence and severity of OIPN and the number of FOLFOX cycles were measured and compared between the two groups. Neurological toxicities were assessed according to the Common Terminology Criteria for Advanced Events, version 3.0. Results: All study patients had OIPN. Most patients experienced grade 1 or 2 sensory neuropathy. Grade 3 sensory neuropathy was observed in two patients in the non-OXY group. All patients in the OXY group completed the scheduled FOLFOX therapy, whereas FOLFOX therapy was discontinued in ten patients in the non-OXY group due to severe peripheral neuropathy. The median numbers of FOLFOX cycles in the OXY and non-OXY groups were 13 (range, 6–46) and 7 (range, 2–18), respectively (P < 0.05). The median cumulative oxaliplatin doses were 1072.3 mg/m2 (range, 408.7–3385.3 mg/m2) in the OXY group and 483.0 mg/m2 (range 76.2–1414.1 mg/m2) in the non-OXY group (P < 0.05). Conclusions: Our findings indicate that CR oxycodone might attenuate the severity of OIPN and extend the use of FOLFOX therapy.

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Incidence of peripheral neuropathy in patients with colorectal cancer receiving oxaliplatin alone vs. radiation therapy and oxaliplatin.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e18281 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e18281-e18281

Author(s):

Matthew Blake Lockwood ◽

Krishna Prasad Joshi ◽

James Mobley ◽

Suneetha Sampath ◽

Eric R Siegel ◽

...

Keyword(s):

Colorectal Cancer ◽

Rectal Cancer ◽

Radiation Therapy ◽

Peripheral Neuropathy ◽

Stage Iv ◽

Sensory Neuropathy ◽

Chi Square ◽

Stage Iv Disease ◽

Nerve Fibrosis ◽

Colorectal Cancer Patients

e18281 Background: Peripheral sensory neuropathy (PN) is a known dose limiting toxicity of oxaliplatin, used to treat patients with colorectal cancer. Patients with rectal cancer receive radiation therapy (RT) in addition to oxaliplatin in adjuvant setting. Pelvic radiation causes plexopathy due to demyelination, ischemia due to blood-vessel injury, and nerve fibrosis. To assess if RT increases the incidence of peripheral neuropathy, we conducted an analysis of patients with colorectal cancer treated with oxaliplatin alone vs. oxaliplatin and radiation. Methods: A retrospective analysis of subjects with stages II, III, and IV rectal (R) and colon (C) cancer from 2005 to 2014 was conducted. Only subjects receiving O with or without RT were included. The incidence of PN was compared for increase in subjects receiving both O and RT compared to O alone via one-sided chi-square tests at 5% alpha, both overall and after subgrouping by stage. Results: Out of 261 subjects analyzed, 158 met the study’s criteria. There were 97 C (all received only O) and 61 R (10 received only O; 51 received O+RT). PN occurred in 37% (19/51) of subjects receiving O+RT compared to 22% (24/107) receiving only O ( P= 0.025). In Stage II-III disease, PN occurred at nearly equal rates of 36% (14/39) in subjects receiving O+RT and 33% (16/46) in subjects receiving O only ( P= 0.457). However, in Stage IV disease, PN occurred in 42% (5/12) of subjects receiving O+RT compared to 13% (8/61) of subjects receiving only O ( P= 0.009). Conclusions: In our study, the incidence of PN was higher in subjects receiving both RT and O compared to O alone. Although our study did not show higher PN in stages II and III disease, patients with rectal cancer may have residual neurotoxicity from previous radiation and the subsequent exposure to oxaliplatin may be contributing to the cumulative toxicity. [Table: see text]

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

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.634 ◽

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.

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Clinical utility of PEG-G-CSF for preventing severe neutropenia in metastatic colorectal cancer patients treated with FOLFOXIRI plus bevacizumab: A single centor retrospective study

10.21203/rs.2.14923/v1 ◽

2019 ◽

Author(s):

Kitagawa Yusuke ◽

Hiroki Osumi ◽

Eiji Shinozaki ◽

Yumiko Ota ◽

Izuma Nakayama ◽

...

Keyword(s):

Colorectal Cancer ◽

Adverse Events ◽

Metastatic Colorectal Cancer ◽

Evaluation Criteria ◽

Progression Free Survival ◽

Severe Neutropenia ◽

Free Survival ◽

The Common ◽

Grade 3 ◽

Colorectal Cancer Patients

Abstract Background: This study aimed to evaluate in clinical practice the efficacy and safety of polyethylene glycol conjugated granulocyte colony-stimulating factor (PEG-G-CSF) for preventing neutropenia in metastatic colorectal cancer (mCRC) patients that received fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab (Bev). Methods: We retrospectively analyzed mCRC patients who received FOLFOXIRI plus Bev between December 2015 and December 2017. We evaluated the efficacy of PEG-G-CSF for treating neutropenia, the overall response rate (ORR) according to the Response Evaluation Criteria in Solid Tumors version 1.1, progression free survival (PFS), overall survival (OS), and adverse events of FOLFOXIRI plus Bev based on the Common Terminology Criteria for Adverse Events version 4.0. Results: A total of 26 patients (median age 53.5 years) were included. The ORR rate was 65.3%, the median PFS was 9.6 months (7.2–16.9), and the median OS was 24.2 months (13.6–NA). Grade 3 or 4 neutropenia occurred in 53.8% of the patients and febrile neutropenia occurred in 7.7%. PEG-G-CSF was given to 77.0% of the patients, including prophylactically (n = 9) and after the development of grade 3 or 4 neutropenia (n = 11). No patients experienced grade 3 or higher neutropenia after the administration of PEG-G-CSF. In seven of the nine patients who received PEG-G-CSF prophylactically (77.7%), no dose adjustment was required.Conclusions: PEG-G-CSF was useful in preventing severe neutropenia in mCRC patients treated with FOLFOXIRI plus Bev.

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A randomized phase II study of modified OPTIMOX1 or FOLFOX in advanced colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.519 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 519-519

Author(s):

C. Mikami

Keyword(s):

Colorectal Cancer ◽

Sensory Neuropathy ◽

Progression Free Survival ◽

Median Number ◽

Stop And Go ◽

Oxaliplatin Treatment ◽

New Strategy ◽

Grade 3 ◽

Colorectal Cancer Patients ◽

Number Of Treatment

519 Background: A combination of leucovorin (LV) and fluorouracil (FU) with oxaliplatin (FOLFOX) is a standard first-line regimen for advanced or unresectable colorectal cancer. Sensory neurotoxicity is its dose-limiting toxicity, but the OPTIMOX1 (stop and go) approach offers a reasonable strategy. This study evaluates a new strategy of intermittent oxaliplatin treatment that is based on FOLFOX4 or modified FOLFOX6 (+/− bevacizumab), a simplified leucovorin and fluorouracil regimen with normal-dose oxaliplatin. Methods: Previously untreated patients were randomly assigned to either FOLFOX administered every 2 weeks until progression (arm FOL) or FOLFOX for six cycles, maintenance without oxaliplatin for six cycles, and continued every six cycles until progression (arm OPT). Results: Sixty patients (arm FOL [n=35], arm OPT [n=33]) were enrolled. The median number of treatment cycles was 10 (range, 3-28) in arm FOL and 12.5 (range, 1-32) in arm OPT. Cumulative dose of oxaliplatin was 850 mg/m2 in arm FOL and 552.5 mg/m2 in arm OPT. Median progression-free survival was 8.5 months in patients allocated to arm FOL compared with 15 months in patients allocated to arm OPT. Response rates evaluated by RECIST criteria were 50% with arm FOL and 64% with arm OPT. National Cancer Institute Common Toxicity Criteria grade 3 toxicity was observed in 37.1% of the patients in arm FOL and 24.0% of patients in arm OPT. Grade 3 sensory neuropathy was observed in 22.8% of the patients in arm FOL and 6% of patients in arm OPT. Conclusions: Our modified OPTIMOX1 regimen may be effective and safe treatment to prevent oxaliplatin-induced neuropathy in advanced or unresectable colorectal cancer patients. No significant financial relationships to disclose.

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Neurological Toxicity in Metastatic Colorectal Cancer Patients Treated with Modified FOLFOX6 plus Bevacizumab

Japanese Clinical Medicine ◽

10.4137/jcm.s15553 ◽

2014 ◽

Vol 5 ◽

pp. JCM.S15553 ◽

Cited By ~ 3

Author(s):

Satoshi Otsu ◽

Yoshinori Hirashima ◽

Kazuo Nishikawa ◽

Hiroyuki Sakashita ◽

Ryotaro Morinaga ◽

...

Keyword(s):

Colorectal Cancer ◽

Adverse Events ◽

Metastatic Colorectal Cancer ◽

Cumulative Dose ◽

Treatment Time ◽

Sensory Neuropathy ◽

Modified Folfox6 ◽

Grade 3 ◽

Median Cumulative Dose ◽

Colorectal Cancer Patients

This study was conducted to investigate the toxicity and efficacy of modified FOLFOX6 plus bevacizumab in patients with metastatic colorectal cancer with particular regard to oxaliplatin-induced neuropathy. Toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) (version 3.0). The evaluation was especially focused on grade 2 oxaliplatin-induced neuropathy. The estimated median treatment time to occurrence of grade 2 sensory neuropathy was 7.3 months. The estimated median cumulative dose to occurrence of grade 2 sensory neuropathy was 931 mg/m2. This study clarified the treatment time from first dose as well as the cumulative dose of oxaliplatin leading to grade 2 neuropathy. It may be important to institute some clinical countermeasures when grade 2 neuropathy occurs so as to reduce the chance of progression to irreversible grade 3 neuropathy.

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XELOX causes less disabling peripheral neuropathy than FOLFOX 4 for Chinese colorectal cancer patients

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.14592 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 14592-14592

Author(s):

T. Yau ◽

P. Chan ◽

J. Tsang ◽

R. Liang ◽

R. Epstein

Keyword(s):

Colorectal Cancer ◽

Peripheral Neuropathy ◽

Cancer Patients ◽

Drug Dosage ◽

Common Side Effect ◽

Outpatient Basis ◽

Neutropenic Sepsis ◽

Phase Ii Studies ◽

Grade 3 ◽

Colorectal Cancer Patients

14592 Background: Infusional 5-FU plus leucovorin and oxaliplatin (FOLFOX4) is an efficacious treatment for colorectal cancer patients in both the adjuvant and metastatic settings. However, around 10% of FOLFOX4 patients will develop with disabling grade 3–4 neuropathy. Recent phase II studies have demonstrated that oral capecitabine in combination with oxaliplatin (XELOX) is as least as effective as FOLFOX4 for colorectal cancer. In this study, we assessed the toxicities of XELOX in Chinese colorectal cancer patients. Methods: Patients who received XELOX at Queen Mary Hospital, Hong Kong between November 2004 and November, 2006 were analyzed. Toxicities were graded by the National Cancer Institute common toxicity system. Results: Thirty-five patients received XELOX on an outpatient basis during the study period: Twenty-four as adjuvant therapy and 11 as treatment for metastatic disease. The most common side effect was grade 1–2 peripheral neuropathy which occurred in 77% of patients. No grade 3–4 neuropathy was reported. Grade 1–2 diarrhea and palmar-plantar erythrodysesthesia (PPE) also occurred in 40 % and 37 % of patients, respectively. The commonest grade 3 toxicities was diarrhea which occurred in 17% of the patients followed by 9% of patients experienced grade 3 PPE. No grade 4 toxicities were reported in our patient’s cohort. Overall, only one (3%) patient had neutropenic sepsis and 36% of patients required 20% reduction in drug dosage. No treatment related death was reported. Conclusions: Our study suggests that XELOX is a well-tolerated and convenient treatment regime. Although mild neuropathy is common in patients receiving XELOX, it causes far less disabling neuropathy than FOLFOX4 in Chinese metastatic colorectal cancer patients. No significant financial relationships to disclose.

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Influence of Postoperative Changes in Sarcopenia on Long-Term Survival in Non-Metastatic Colorectal Cancer Patients

Cancers ◽

10.3390/cancers13102410 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2410

Author(s):

Chungyeop Lee ◽

In-Ja Park ◽

Kyung-Won Kim ◽

Yongbin Shin ◽

Seok-Byung Lim ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Cancer Patients ◽

Medical Center ◽

The Body ◽

Term Survival ◽

Postoperative Changes ◽

Asan Medical ◽

Colorectal Cancer Patients

The effect of perioperative sarcopenic changes on prognosis remains unclear. We conducted a retrospective cohort study with 2333 non-metastatic colorectal cancer patients treated between January 2009 and December 2012 at the Asan Medical Center. The body composition at diagnosis was measured via abdominopelvic computed tomography (CT) using Asan-J software. Patients underwent CT scans preoperatively, as well as at 6 months–1 year and 2–3 years postoperatively. The primary outcome was the association between perioperative sarcopenic changes and survival. According to sarcopenic criteria, 1155 (49.5%), 890 (38.2%), and 893 (38.3%) patients had sarcopenia preoperatively, 6 months–1 year, and 2–3 years postoperatively, respectively. The 5-year overall survival (OS) (95.8% vs. 92.1%, hazard ratio (HR) = 2.234, p < 0.001) and 5-year recurrence-free survival (RFS) (93.2% vs. 86.2%, HR = 2.251, p < 0.001) rates were significantly lower in patients with preoperative sarcopenia. Both OS and RFS were lower in patients with persistent sarcopenia 2–3 years postoperatively than in those who recovered (OS: 96.2% vs. 90.2%, p = 0.001; RFS: 91.1% vs. 83.9%, p = 0.002). In multivariate analysis, postoperative sarcopenia was confirmed as an independent factor associated with decreased OS and RFS. Pre- and postoperative sarcopenia and changes in the condition during surveillance were associated with oncological outcomes.

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