Immediate Adjuvant Chemotherapy in Non-Metastatic Colon Cancer: Phase I Trial Evaluating a Novel Treatment Protocol

2021 ◽  
Author(s):  
Jafari Mehraneh D ◽  
Carmichael Joseph C ◽  
Dayyani Farshid ◽  
McKinney Chelsea ◽  
Wenzel Lari ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Phase I ◽  
Phase I Trial ◽  
Treatment Protocol ◽  
Metastatic Colon Cancer ◽  
Novel Treatment

A National Cancer Database (NCDB) analysis of the impact of nonmetastatic colon cancer sidedness on survival.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 139-139
Author(s):  
Deven Patel ◽  
Timothy DiPeri ◽  
Brian Cox ◽  
Andrew Eugene Hendifar ◽  
Arsen Osipov ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Logistic Regression ◽  
Adjuvant Chemotherapy ◽  
Large Population ◽  
Stage I ◽  
Prognostic Impact ◽  
Metastatic Colon Cancer ◽  
Prognostic Features ◽  
Binomial Logistic Regression ◽  
The Impact

139 Background: Differences in embryological origin and tumor biology distinguish right-sided colon cancer (RCC) from left-sided colon cancer (LCC). Previous studies characterizing the prognostic impact of colon cancer laterality on clinical outcomes in non-metastatic colon cancer have been conflicting, thus closer examination is needed. Methods: Using the NCDB, patients with stage I-III colon cancer between 2004-2014 were stratified according to tumor location; RCC vs. LCC. Patient (pt) and tumor characteristics were compared in univariate analysis, survival (OS) was estimated by Kaplan-Meier (KM) curves and Cox proportional hazards modeling. Binomial logistic regression analysis was utilized to identify variables associated with colon cancer laterality. Results: Of the 342,735 pts who met inclusion criteria, 210,343 (61.4%) were diagnosed with RCC, and 132,392 (38.6%) with LCC. Pts with RCC were older (mean 71.6 vs. 66.4 years, p< 0.001) and predominantly female (65% vs. 35%, p< 0.001) compared to those with LCC. A trend towards poorer OS was seen in pts with RCC (mean 91.0 mos [95% CI: 90.2-91.8]) compared to LCC (112.2 mos [95% CI: 110.9-113.6]) in unadjusted analysis. On Cox multivariable adjusted analyses there was a significant but minimal impact on OS and laterality (hazard ratio or HR [LCC as ref] 0.978, 95% CI 0.967-0.989 p< 0.0001). Multiple unadjusted KM survival analyses showed RCC with T4 disease, high-grade, LVI/PNI, positive margins, N0-N2 disease, tumor deposits, and receipt of adjuvant chemotherapy had poorer OS than those features in LCC (all p < 0.0001). Binomial logistic regression showed RCCs were significantly more likely to be higher grade (odds ratio or OR 2.024) and MSI-H (OR 2.010) with trends (nonsignificant) towards more likely having N1-2 positive disease, LVI, less receipt of adjuvant chemotherapy, and fewer tumor deposits. Conclusions: The impact of sidedness on prognosis in stage I-III colon cancer is complex. In this large, population-based study, RCC tends to be associated with more adverse prognostic features than LCC. More investigation into the biologic differences between RCC and LCC is warranted and how they impact phenotype and survival.

Phase I Trial of Intravenous Thymidine and Carboplatin in Patients With Advanced Cancer

1999 ◽  
Vol 17 (9) ◽  
pp. 2922-2922 ◽  
Author(s):  
H. Ian Robins ◽  
Kendra Tutsch ◽  
Doerthe M. Katschinski ◽  
Elaine Jacobson ◽  
Minesh Mehta ◽  
...  
Keyword(s):  
Phase I ◽  
Dose Level ◽  
Phase I Trial ◽  
Combined Therapy ◽  
High Grade Glioma ◽  
Maximum Tolerated Dose ◽  
Metastatic Colon Cancer ◽  
Minor Response ◽  
The North ◽  
A Minor

PURPOSE: To evaluate the biologic interactions and toxicities of carboplatin combined with a 24-hour infusion of thymidine 75 mg/m2 in a phase I trial. PATIENTS AND METHODS: Thirty-two patients with cancer refractory to conventional therapy were treated. The first set of patients (n = 7) received thymidine alone 4 weeks before subsequent planned courses of thymidine combined with carboplatin followed (4 weeks) by carboplatin alone. Carboplatin was administered over 20 minutes at hour 20 of the 24-hour thymidine infusion. The carboplatin dose was escalated in patient groups: 200 mg/m2 (n = 3); 300 mg/m2 (n = 7); 350 mg/m2 (n = 4); 400 mg/m2 (n = 3); 480 mg/m2 (n = 10); and 576 mg/m2 (n = 5). At the maximum-tolerated dose (480 mg/m2), five patients received combined therapy first and carboplatin alone second, and five patients received carboplatin first and combined therapy second. Maintenance therapy for stable or responding patients was combined therapy. RESULTS: Evaluation demonstrated a trend toward thymidine protection of carboplatin-induced treatment-limiting thrombocytopenia. Neutropenia with carboplatin alone or in combination was negligible. Thymidine alone had no myelosuppressive effects and produced reversible grade 1 or 2 nausea and vomiting (57%), headache (25%), and grade 1 neurotoxicity (22%). Thymidine did not enhance expected carboplatin toxicities. There was no therapy-related infection or bleeding. Analysis of platinum in plasma ultrafiltrate and urine showed no effect by thymidine. Similarly, thymidine pharmacokinetics was not affected by carboplatin. As predicted, nicotinamide adenine dinucleotide levels in peripheral lymphocytes were increased during exposure to carboplatin and/or thymidine but were decreased by carboplatin alone. In three patients with high-grade glioma, responses included one complete remission (21 months) and one partial remission (14 months) at the 480-mg/m2-dose level, and disease stabilization (7 months) at the 400-mg/m2-dose level. A minor response was observed in a patient with metastatic colon cancer (5 months) at the 480-mg/m2-dose level. CONCLUSION: The combination of carboplatin and thymidine as described is well tolerated. The data presented have resulted in a phase II study by the North American Brain Tumor Consortium.

A phase I trial of a multi-epitope cancer vaccine (EP-2101) in non-small cell lung (NSCLC) and colon cancer patients

2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 2525-2525 ◽  
Author(s):  
G. Y. Ishioka ◽  
M. L. Disis ◽  
M. A. Morse ◽  
C. C. Cunningham ◽  
H.-J. Lenz ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Phase I ◽  
Cancer Patients ◽  
Cancer Vaccine ◽  
Phase I Trial ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals A phase I trial of immediate postoperative intraperitoneal floxuridine and leucovorin plus systemic 5-fluorouracil and levamisole after resection of high risk colon cancer

Cancer ◽  
1994 ◽  
Vol 74 (8) ◽  
pp. 2224-2233 ◽  
Author(s):  
David P. Kelsen ◽  
Leonard Saltz ◽  
Alfred M. Cohen ◽  
T. J. Yao ◽  
Warren Enker ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Phase I ◽  
Phase I Trial

scholarly journals Clinical activity of patupilone in patients with pretreated advanced/metastatic colon cancer: results of a phase I dose escalation trial

2011 ◽  
Vol 105 (11) ◽  
pp. 1646-1653 ◽  
Author(s):  
B Melichar ◽  
E Casado ◽  
J Bridgewater ◽  
J Bennouna ◽  
M Campone ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Phase I ◽  
Dose Escalation ◽  
Clinical Activity ◽  
Metastatic Colon Cancer

Transient increase in serum CEA while on adjuvant chemotherapy for colon cancer: Is this of prognostic importance?

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 654-654
Author(s):  
Nicola Jane Mitchell ◽  
Victoria Hinder ◽  
Melissa Murray ◽  
Jerome Macapagal ◽  
Paul Ivan Thompson ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Cox Regression ◽  
Transient Increase ◽  
Stage Ii ◽  
Response To Treatment ◽  
Metastatic Colon Cancer ◽  
Continuous Increase ◽  
Significant Difference ◽  
Serum Carcinoembryonic Antigen

654 Background: Serum Carcinoembryonic Antigen (CEA) is used to monitor response to treatment in metastatic colon cancer. Transient surges in CEA can occur after initiation of chemotherapy and are not associated with worse outcome. There is little data on transient CEA surge in the adjuvant setting. We aimed to review patterns of change in CEA levels with adjuvant chemotherapy and investigate associations between transient rises and patient survival. Methods: A retrospective review of patients in Auckland with a new diagnosis of colon cancer in 2001 or 2005 was reported previously [Murray, NZMJ, 2011]. CEA results immediately pre-chemotherapy, during and up to 9 months post chemotherapy were collected and death data was updated. Increase in CEA during chemotherapy was measured as the maximum change from baseline; values more than 2 (within-person) standard deviations above baseline [Erden, Scand, J Clin Lab Inv, 2008] were classified as increased. An increase was transient if the last recorded CEA post chemotherapy was within 2 sd of baseline. Three patient groups were defined: NI (no increase in CEA); TI (transient increase in CEA); and CI (continuous increase in CEA). Kaplan-Meier methods were used to estimate 5-year survival; Cox regression and log-rank p-values were used to compare survival. Results: Of the 77 patients identified with stage II or III disease who had received adjuvant chemotherapy, 61 had sufficient CEA data to be included. The TI group were younger (median [quartiles]: TI 59 [54, 64]; NI 65 [53, 74]; CI 68 [62, 74]) but a greater proportion were stage II (TI 32%; NI 23%; CI 17%). Patients were followed up for a minimum of 7.3 years (or death). Number of deaths per group were: TI 3/19; NI 9/30; CI 7/12. The 5 year overall survival was: TI 95%; NI 83%; CI 42%. There was no significant difference between TI and NI (p = 0.1), but the confidence interval was wide (HR 0.3; 95% CI (0.07 to 1.5). For CI compared to NI, the HR was 2.8 (95% CI (1.0 to 7.6), p = 0.04). Conclusions: The observation that CEA surge does not signal poorer prognosis will be further examined as part of a separate population-based New Zealand-wide study of colorectal cancer diagnosis, treatment and outcome. Part funded by a Genesis Oncology Trust grant.

Time to adjuvant chemotherapy in CEA-positive colon cancer: An NCDB analysis.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 603-603
Author(s):  
Yang Zhang ◽  
Sarah J Aurit ◽  
Mohan Satish ◽  
Eugene Chau ◽  
Peter T. Silberstein
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Optimal Timing ◽  
Metastatic Colon Cancer ◽  
Risk Of Death ◽  
Increased Risk ◽  
Serum Carcinoembryonic Antigen ◽  
Test Result

603 Background: It is well accepted that positive serum carcinoembryonic antigen (CEA) levels are associated with inferior survival in patients with advanced non-metastatic colon cancer; however, it is not fully elucidated whether this prognostic factor can inform clinical decisions, specifically for the optimal timing of adjuvant chemotherapy after definitive surgical treatment. This study was aimed to determine the relationship between onset of adjuvant chemotherapy and rate of survival in stage III colon cancer patients who tested CEA-positive, and thus, potentially identifying the optimal timing to increase survivorship. Methods: We identified 19,180 patients from the NCDB with TNM pathologic stage IIIB and IIIC adenocarcinoma of the colon who also had a recorded CEA test result and whom had received adjuvant chemotherapy. We examined unadjusted overall survival based on CEA status with the Kaplan-Meier method. A multivariable Cox regression model was estimated to determine the association of CEA status and overall survival after controlling for site, stage, days from surgery to chemotherapy, demographic background, and facility characteristics. All analyses were conducted with SAS version 9.4 (SAS Institute Inc., Cary, NC) with a statistical threshold of p < 0.05. Results: Based on the log-rank χ2 test, a positive CEA test result was significantly associated with worse survival. We adjusted for patient and facility level characteristics, and found a 49.7% increased risk of death for a patient with a positive CEA result (95% CI: 41.7% to 58.2%). We found a median number of 43 days from definitive surgery to initiation of chemotherapy; after adjusting for all other variables, we found for every ten-day delay in receiving adjuvant therapy after definitive surgical intervention, there was a 1.6% increased risk of death (95% CI: 1.0 to 2.2%). Conclusions: In this cohort of patients who tested CEA-positive, delays in receiving adjuvant chemotherapy had a negative linear association on survival. Adjuvant therapy should be considered as soon as patient’s clinical condition permits.

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