Neuropathy severity at the time of oxaliplatin treatment alteration in patients with colon cancer (Alliance A151912)

88 Background: Splenic enlargement has been reported in patients treated with oxaliplatin. However, the characteristics of oxaliplatin-induced splenomegaly were not well studied. Here we evaluated the change of splenic volume and its clinical significance in patients treated by oxaliplatin-based regimen. Methods: Patients with stage II-IV primary colon cancer treated with oxaliplatin and capecitabine in China National Cancer Center from January 2016 to December 2017 were screened for this retrospective study. Those with complete laboratory tests and computed tomographic data before, during and up to 1.5 years after the chemotherapy were selected. The splenic size was measured by AWVolumeshare5. Splenomegaly was defined as an over 30% increase of splenic size from baseline. Recovery of splenomegaly was defined as the splenic size fell back to a 0.9 to1.1-fold range of baseline. Results: Out of a total of 144 patients, 102 (70.8%) had over 30% increase, 72 (50.0%) had over 50% increase, and 22 (15.3%) had over 100% increase in splenic size after oxaliplatin-based regimen. Among the 102 splenomegaly patients, 5 (4.9%) develop splenomegaly within 3 chemotherapy cycles, 53 (53.0%) within 6 cycles, 73 (71.6%) within 9 cycles, and 102 (100.0%) within 3 months after the last administration of oxaliplatin. Compared to the group without splenomegaly, patients with splenomegaly received more cycles of oxaliplatin administrations (median 8 vs 6, p < 0.001) and greater dose intensity (total dose per square meter) (median 822.8mg/m2 vs 629.3mg/m2, p < 0.001). Patients with splenomegaly had higher incidence of thrombocytopenia (61.7% vs 38.1%, p = 0.009) and are more likely to undergo oxaliplatin dose reduction due to thrombocytopenia (21.6% vs 7.1%, p = 0.038). The recovery rates of splenic size within 0.5, 1 and 1.5 years after the end of oxaliplatin treatment were 23.2%, 50.6% and 74.3%, respectively. Conclusions: Splenomegaly are common in patients treated with oxaliplatin-based chemotherapy, and most would recover in 1.5 years after completion of therapy. Patients with splenomegaly are prone to experience thrombocytopenia and oxaliplatin dose reduction. Further studies are needed to reveal the mechanism how oxaliplatin induce splenomegaly.

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Patient-specific meta-analysis of 3 validation studies of the 12-gene colon cancer recurrence score assay for recurrence risk assessment after surgery with or without 5FU and oxaliplatin.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.3599 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 3599-3599

Author(s):

Greg Yothers ◽

Alan P. Venook ◽

Takeharu Yamanaka ◽

Yan Lin ◽

Michael Crager ◽

...

Keyword(s):

Colon Cancer ◽

Meta Analysis ◽

Recurrence Score ◽

Recurrence Risk ◽

Current Medical ◽

Stage Ii ◽

Patient Specific ◽

Risk Estimates ◽

Oxaliplatin Treatment ◽

Current Medical Practice

3599 Background: The 12-gene Oncotype DX Colon Recurrence Score assay is a clinically validated genomic assay that evaluates recurrence risks in stage II and stage III colon cancer patients independent of clinical-pathologic features. Improved colon cancer care has reduced recurrence rates since the late 1990’s. Methods: Pre-specified patient-specific meta-analysis methods were used to estimate 1-, 3- and 5-year recurrence risk combining the 12-gene colon recurrence score (RS) validation studies CALGB 9581, NSABP C-07 and SUNRISE. Cox models had effects for RS result, number of nodes examined (<12 or ≥ 12), T-stage, MMR status, and stage (II, IIIAB or IIIC). Baseline cumulative hazard estimates used the latest two studies to reflect current medical practice. Estimates for surgery, surgery+5FU and surgery+5FU+oxaliplatin treatment were provided by integrating stage-specific 5FU hazard ratios from a meta-analysis of the QUASAR study (2007) and a pooled analysis of NSABP studies (Wilkinson 2010), and oxaliplatin treatment effect estimates from NSABP C-07. Recurrence risk with 5FU alone was not estimated for MMR-deficient patients due to expected lack of 5FU efficacy in these patients (Sargent 2010). Results: In the overall population of 2,179 patients, 55%, 32% and 13% were Stage II, IIIA/B and IIIC, 63% had ≥12 nodes examined, 90% were T3, and 88% were MMR proficient. Median RS result was 31 (IQR 23–39). RS result and each clinical-pathologic factor contributed independent prognostic information (meta-analysis Wald tests, all p<.001). Risk estimates are generally lower than previous RS report risk estimates. For patients with pathological stage II, T3, MMR-proficient tumors with ≥12 nodes examined, approximately 40% are expected to have 5-year recurrence risk ≤10% with surgery alone based on the distribution of RS results. The table shows example 5-year recurrence risk estimates for specific RS results and clinical-pathologic characteristics. Conclusions: The new recurrence risk estimates provide more patient-specific information reflecting more current medical practice than previous reports using RS result, allowing better, more individualized treatment decisions.[Table: see text]

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Comparative proteomic analysis of colon cancer cells in response to Oxaliplatin treatment

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics ◽

10.1016/j.bbapap.2009.06.005 ◽

2009 ◽

Vol 1794 (10) ◽

pp. 1433-1440 ◽

Cited By ~ 21

Author(s):

Yi Yao ◽

Xiao-Yuan Jia ◽

Hong-Yu Tian ◽

Yu-Xiang Jiang ◽

Gen-Jun Xu ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Proteomic Analysis ◽

Colon Cancer Cells ◽

Comparative Proteomic Analysis ◽

Oxaliplatin Treatment

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Clinical Outcome From Oxaliplatin Treatment in Stage II/III Colon Cancer According to Intrinsic Subtypes

JAMA Oncology ◽

10.1001/jamaoncol.2016.2314 ◽

2016 ◽

Vol 2 (9) ◽

pp. 1162 ◽

Cited By ~ 73

Author(s):

Nan Song ◽

Katherine L. Pogue-Geile ◽

Patrick G. Gavin ◽

Greg Yothers ◽

S. Rim Kim ◽

...

Keyword(s):

Colon Cancer ◽

Clinical Outcome ◽

Stage Ii ◽

Intrinsic Subtypes ◽

Oxaliplatin Treatment

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miR-34a Regulates Multidrug Resistance via Positively Modulating OAZ2 Signaling in Colon Cancer Cells

Journal of Immunology Research ◽

10.1155/2018/7498514 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 11

Author(s):

Yong Li ◽

Ping Gong ◽

Ji-xue Hou ◽

Wei Huang ◽

Xiao-ping Ma ◽

...

Keyword(s):

Colon Cancer ◽

Multidrug Resistance ◽

Cellular Response ◽

Critical Role ◽

Ectopic Expression ◽

Multidrug Resistant ◽

Chemotherapeutic Agents ◽

Aberrant Expression ◽

Oxaliplatin Treatment ◽

Histoculture Drug Response Assay

Although aberrant expression of miR-34a, an essential tumor suppressor miRNA, has been frequently observed in colon cancer (CCa), whether miR-34a can regulate CCa progression by modulating other facets of this malignancy (such as multidrug resistance, MDR) remains unknown. Here, we report for the first time that miR-34a expression was significantly downregulated in clinical CCa samples from oxaliplatin-resistant patients and in experimentally established multidrug-resistant CCa cells. By using histoculture drug response assay, we further confirmed that clinical CCa samples with lower miR-34a expression appeared to be more resistant to chemotherapy. Functionally, ectopic expression of exogenous miR-34a resensitized multidrug-resistant HCT-8/OR cells to oxaliplatin treatment, whereas miR-34a inhibition augmented the oxaliplatin resistance in chemosensitive HCT-8 cells. Mechanistically, miR-34a positively regulated the mRNA stability of the ornithine decarboxylase antizyme 2 (OAZ2) by directly targeting its three prime untranslated region (3′UTR). Consequently, suppression of the expression of miR-34a/OAZ2 signaling by chemotherapeutic agents significantly enhanced the activation of MDR-associated ATP-binding cassette (ABC) transporters and antiapoptosis pathways, thus leading to MDR development in CCa cells. Collectively, our combined analysis reveals a critical role of miR-34a/OAZ2 cascade in conferring a proper cellular response to CCa chemotherapy.

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Neuropathy Severity at the Time of Oxaliplatin Treatment Alteration in Patients with Colon Cancer (Alliance A151912)

10.21203/rs.3.rs-300187/v1 ◽

2021 ◽

Author(s):

Daniel Hertz ◽

Travis J Dockter ◽

Daniel V Satele ◽

Charles L Loprinzi ◽

Jennifer G Le-Rademacher

Keyword(s):

Colon Cancer ◽

Peripheral Neuropathy ◽

Dose Reduction ◽

Clinical Use ◽

Chemotherapy Treatment ◽

Oxaliplatin Treatment ◽

End Of Treatment ◽

Patient Reported ◽

Few Data ◽

Group 1

Abstract Background: Clinical guidelines recommend altering chemotherapy treatment by decreasing, delaying, or discontinuing dosing in patients who are experiencing chemotherapy-induced peripheral neuropathy. There are few data available on the clinical use of treatment alteration including the severity of CIPN at the time of treatment alteration. Methods: This was a retrospective analysis of patients receiving oxaliplatin on the NCCTG N08CB trial. Neuropathy severity was assessed at each cycle by clinicians and patients. Patients were classified as 1) completed treatment without alteration, 2) dose reduction or delay due to neuropathy, 3) discontinuation due to neuropathy, or discontinuation for other toxicity (4), or another reason (5). Comparisons focused primarily on patients with alteration due to neuropathy (groups 2 and/or 3) compared with patients who completed treatment without alteration (group 1). Results: In 350 participants, 135 (39%) completed treatment without alteration, 70 (20%) had a dose reduction or delay due to neuropathy, and 35 (10%) discontinued early due to neuropathy. Clinician-assessed neuropathy severity was greater in patients at the time of dose reduction or delay compared with severity at the end of treatment in patients without alteration (p<0.0001). Patient-reported neuropathy severity at cycle 4 was worse in patients who had an alteration as compared with patients who completed treatment without alteration (p=0.017). Conclusions: Treatment alterations due to neuropathy are common in patients receiving oxaliplatin for colon cancer and are associated with clinician-assessed neuropathy severity. Rapid increases in patient-reported neuropathy severity indicate a potential need for monitoring and intervention.

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Neuropathy severity at the time of oxaliplatin treatment alteration in patients with colon cancer (Alliance A151912).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.12090 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 12090-12090

Author(s):

Daniel Louis Hertz ◽

Travis Dockter ◽

Daniel V. Satele ◽

Charles L. Loprinzi ◽

Jennifer Le-Rademacher

Keyword(s):

Colon Cancer ◽

Peripheral Neuropathy ◽

Dose Reduction ◽

Oxaliplatin Treatment ◽

End Of Treatment ◽

Chi Squared ◽

Few Data ◽

Eortc Qlq ◽

To Receive ◽

Clinical Trial Information

12090 Background: Clinical guidelines recommend altering chemotherapy treatment by decreasing, delaying, or discontinuing dosing in patients (pts) experiencing chemotherapy-induced peripheral neuropathy (CIPN). There are few data available on clinical use of treatment alteration including the severity of CIPN at the time of alteration. Our objective was to investigate the incidence of oxaliplatin treatment alterations and CIPN severity at that time. Methods: This was a retrospective analysis of pts with colon cancer scheduled to receive oxaliplatin-containing combination chemotherapy on the N08CB trial of intravenous calcium and magnesium for prevention of CIPN. Dose alterations were not mandated by the N08CB protocol. Clinicians assessed CIPN using NCI-CTCAE V.4.0; pts used the sensory subscale of the EORTC-QLQ Chemotherapy-Induced Peripheral Neuropathy 20 (CIPN8). Pts were classified as 1) completed oxaliplatin treatment without alteration, 2) dose reduction or delay due to CIPN, 3) discontinuation due to CIPN, 4) discontinuation due to other AE, or 5) discontinuation for another reason. Comparisons focused primarily on pts with alteration due to CIPN (groups 2 and/or 3) compared with pts completing treatment without alteration (group 1) using chi-squared and Kruskal-Wallis tests. Results: In this analysis of 350 N08CB pts, 135 (39%) completed oxaliplatin without treatment alteration, 70 (20%) had a dose reduction (n=66) or delay (n=4) due to CIPN and 35 (10%) discontinued early due to CIPN. Pts who experienced alterations due to CIPN were younger (p=0.0249) and more likely to be female (p=0.008). Clinician-assessed CIPN severity was greater in pts at the time of dose reduction or delay compared with CIPN severity at the end of treatment in pts with no alteration (p<0.0001). Pt-assessed CIPN severity was not different in pts who completed treatment without alteration compared to pts who had a dose reduction or delay (p=0.88) or a discontinuation (p=0.37). CIPN8 scores at cycle 4 were higher (worse) in pts who eventually had any alteration (i.e., reduction, delay, or discontinuation) compared to pts who completed treatment without any alteration (median CIPN8 11.5 vs. 7.7, p=0.023). Conclusions: Treatment alterations due to CIPN are relatively common in pts receiving adjuvant oxaliplatin for colon cancer and are associated with clinician-assessed but not pt-reported CIPN severity. Rapid CIPN8 increases early in treatment are indicative of increased likelihood of a future oxaliplatin treatment alteration, indicating a potential use of early monitoring and intervention. Support: UG1CA189823; https://acknowledgments.alliancefound.org. Clinical trial information: NCT01099449 (NCCTG N08CB).

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Anthocyanin-rich extract from black rice inhibits colon cancer formation in mice

Cell Biology International ◽

10.1042/cbi034s044d ◽

2010 ◽

Vol 34 (8) ◽

pp. S44-S44

Author(s):

Bo Dong ◽

Xinmei Zhou ◽

Xun Xu ◽

Huang Xu ◽

Yongxia Zheng ◽

...

Keyword(s):

Colon Cancer ◽

Black Rice

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