scholarly journals The Value of New Chemotherapeutic Agents for Metastatic Colorectal Cancer

2010 ◽  
Vol 170 (6) ◽  
pp. 537 ◽  
Author(s):  
David H. Howard
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Chemotherapeutic Agents ◽  
New Chemotherapeutic Agents

Therapeutic Armamentarium in Metastatic Colorectal Cancer

2009 ◽  
Vol 05 (01) ◽  
pp. 48
Author(s):  
Teresa Macarulla ◽  
Ben Markman ◽  
Josep Tabernero ◽  
◽  
◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Median Overall Survival ◽  
Molecular Targets ◽  
Chemotherapeutic Agents ◽  
Biologic Therapies ◽  
Metastatic Setting ◽  
Angiogenesis Process ◽  
New Treatments ◽  
New Chemotherapeutic Agents

Colorectal cancer is one of the most frequently diagnosed malignancies in both men and women and, despite recent advances, the prognosis in the metastatic setting remains poor. In the last decade the introduction of new chemotherapeutic agents has improved the median overall survival of these patients. The demonstration that deregulation and/or activation of selected kinase proteins are common phenomena in patients with colon cancer has prompted the development of new biologic therapies targeting such proteins. Further, inhibition of the angiogenesis process can result in efficacy advantage. To date, three targeted therapies have been approved for the treatment of patients with metastatic colorectal cancer: bevacizumab, cetuximab and panitumumab. New treatments directed against other molecular targets are being developed in order to improve these results.

scholarly journals IL15RA and SMAD3 Genetic Variants Predict Overall Survival in Metastatic Colorectal Cancer Patients Treated with FOLFIRI Therapy: A New Paradigm

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1705
Author(s):  
Elena De Mattia ◽  
Jerry Polesel ◽  
Rossana Roncato ◽  
Adrien Labriet ◽  
Alessia Bignucolo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Prognostic Score ◽  
Chemotherapeutic Agents ◽  
Rank Test ◽  
P Value ◽  
Genetic Determinants ◽  
New Paradigm

A new paradigm in cancer chemotherapy derives from the interaction between chemotherapeutics, including irinotecan and 5-fluorouracil (5-FU), and the immune system. The patient’s immune response can modulate chemotherapy effectiveness, and, on the other hand, chemotherapeutic agents can foster tumor cell immunogenicity. On these grounds, the analysis of the cancer patients’ immunogenetic characteristics and their effect on survival after chemotherapy represent a new frontier. This study aims to identify genetic determinants in the immuno-related pathways predictive of overall survival (OS) after FOLFIRI (irinotecan, 5-FU, leucovorin) therapy. Two independent cohorts comprising a total of 335 patients with metastatic colorectal cancer (mCRC) homogeneously treated with first-line FOLFIRI were included in the study. The prognostic effect of 192 tagging genetic polymorphisms in 34 immune-related genes was evaluated using the bead array technology. The IL15RA rs7910212-C allele was associated with worse OS in both discovery (HR: 1.57, p = 0.0327, Bootstrap p-value = 0.0280) and replication (HR:1.71, p = 0.0411) cohorts. Conversely, SMAD3 rs7179840-C allele was associated with better OS in both discovery (HR:0.65, p = 0.0202, Bootstrap p-value = 0.0203) and replication (HR:0.61, p = 0.0216) cohorts. A genetic prognostic score was generated integrating IL15RA-rs7910212 and SMAD3-rs7179840 markers with inflammation-related prognostic polymorphisms we previously identified in the same study population (i.e., PXR [NR1I2]-rs1054190, VDR-rs7299460). The calculated genetic score successfully discriminated patients with different survival probabilities (p < 0.0001 log-rank test). These findings provide new insight on the prognostic value of genetic determinants, such as IL15RA and SMAD3 markers, and could offer a new decision tool to improve the clinical management of patients with mCRC receiving FOLFIRI.

Efficacy of palliative chemotherapy in elderly patients with colorectal cancer

2019 ◽  
Vol 57 (04) ◽  
pp. 484-490
Author(s):  
Wolfram Bohle ◽  
Amelie Pachlhofer ◽  
Wolfram Zoller
Keyword(s):  
Colorectal Cancer ◽  
Multivariate Analysis ◽  
Elderly Patients ◽  
Metastatic Colorectal Cancer ◽  
Primary Tumor ◽  
Palliative Chemotherapy ◽  
Age Groups ◽  
Chemotherapeutic Agents ◽  
Old Patients ◽  
The Impact

Abstract Background The number of old patients suffering from colorectal cancer rises. In clinical trials, old patients are underrepresented, and chemotherapy is significantly less often performed in elderly patients. We analyzed the impact of elder age for palliative chemotherapy in patients suffering from metastatic colorectal cancer, according to therapeutic drugs used, intensity of treatment performed, and therapeutic results. Materials and methods We analyzed consecutive patients with metastatic colorectal cancer treated in palliative intention in our department. Assessed data included age (</> 75 years), sex, comorbidity, site of primary tumor, k-ras-status, site and amount of metastasis, number and kind of chemotherapeutic agents used, number of consecutive therapy lines performed, dose intensity, toxicity, time between start and end of palliative chemotherapy, and overall survival. Prognostic variables were tested in uni- and multivariate analysis. Results Ninety-seven patients (69 < 75, 18 > 75 years) were included. Age groups were well balanced according to site of primary tumor, k-ras-mutational status, localization, and number of metastatic sites. Cardial and renal comorbidity was more frequent in elderly patients. The median number of chemotherapeutic drugs used and lines of therapy performed did not differ between age groups, except of oxaliplatin, which was significantly less often used in old patients. Median survival did not differ between age groups (23.4 vs. 23.5 months). In multivariate analysis, only left-sided primary tumor and more than 3 lines of therapy performed were prognostic positive variables. Conclusion Old patients can profit from palliative chemotherapy to the same extent as younger ones.

scholarly journals Chemotherapy in the Setting of Severe Liver Dysfunction in Patients with Metastatic Colorectal Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-7
Author(s):  
Pashtoon Murtaza Kasi ◽  
Gita Thanarajasingam ◽  
Heidi D. Finnes ◽  
Jose C. Villasboas Bisneto ◽  
Joleen M. Hubbard ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Liver Dysfunction ◽  
Chemotherapeutic Agents ◽  
Biologic Agents ◽  
Biologic Agent ◽  
Severe Liver ◽  
Severe Liver Dysfunction ◽  
Ras Status ◽  
Doublet Chemotherapy

The liver is the dominant site of metastases for patients with metastatic colorectal cancer (mCRC). Depending on the timing of diagnosis and the biology of the disease, it is not uncommon for these patients to present with visceral crisis in the form of severe liver dysfunction. Treatment of these individuals is, however, difficult and challenging. The decision to consider chemotherapy in these dire circumstances entails consideration of numerous factors. If we were to focus on just the metabolism of the different drugs and biologic agents available to treat mCRC, both 5-fluorouracil and oxaliplatin alone or in combination with a monoclonal antibody are reasonable choices. Specifically, FOLFOX is a feasible and safe option in patients with mCRC with severe liver dysfunction. Choice of the biologic agent to add to the doublet chemotherapy could be individualized based on the RAS status and the clinical scenario. Based on the divergent experience of treating 2 cases and other prior reports, a summary of recommendations with a model in the form of a “therapeutic triad” is presented. The paper highlights the therapeutic challenges in patients with mCRC and severe liver dysfunction. The choice of chemotherapeutic agents and reports of other cases/series is also presented.

scholarly journals Optimising the use of cetuximab in the continuum of care for patients with metastatic colorectal cancer

ESMO Open ◽  
2018 ◽  
Vol 3 (4) ◽  
pp. e000353 ◽  
Author(s):  
Richard M Goldberg ◽  
Clara Montagut ◽  
Zev A Wainberg ◽  
Philippe Ronga ◽  
François Audhuy ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Growth Factor Receptor ◽  
Standard Of Care ◽  
Excisional Biopsy ◽  
Continuum Of Care ◽  
Chemotherapeutic Agents ◽  
Treatment Benefit ◽  
Epidermal Growth ◽  
Additional Clinical Benefit

The anti-epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab in combination with chemotherapy is a standard of care in the first-line treatment ofRASwild-type (wt) metastatic colorectal cancer (mCRC) and has demonstrated efficacy in later lines. Progressive disease (PD) occurs when tumours develop resistance to a therapy, although controversy remains about whether PD on a combination of chemotherapy and targeted agents implies resistance to both components. Here, we propose that some patients may gain additional clinical benefit from the reuse of cetuximab after having PD on regimens including cetuximab in an earlier treatment line. We conducted a non-systematic literature search in PubMed and reviewed published and ongoing clinical trials, focusing on later-line cetuximab reuse in patients with mCRC. Evidence from multiple studies suggests that cetuximab can be an efficacious and tolerable treatment when continued or when fit patients with mCRC are retreated with it after a break from anti-EGFR therapy. Furthermore, on the basis of available preclinical and clinical evidence, we propose that longitudinal monitoring ofRASstatus may identify patients suitable for such a strategy. Patients who experience progression on cetuximab plus chemotherapy but have maintainedRASwt tumour status may benefit from continuation of cetuximab with a chemotherapy backbone switch because they have probably developed resistance to the chemotherapeutic agents rather than the biologic component of the regimen. Conversely, patients whose disease progresses on cetuximab-based therapy due to drug-selected clonal expansion ofRAS-mutant tumour cells may regain sensitivity to cetuximab following a defined break from anti-EGFR therapy. Looking to the future, we propose thatRASstatus determination at disease progression by liquid, needle or excisional biopsy may identify patients eligible for cetuximab continuation and rechallenge. With this approach, treatment benefit can be extended, adding to established continuum-of-care strategies in patients with mCRC.

Nonagenarian patients with metastatic colorectal cancer: Results from the South Australian metastatic colorectal cancer registry.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 752-752 ◽  
Author(s):  
Timothy Jay Price ◽  
Christos Stelios Karapetis ◽  
Cynthia Piantadosi ◽  
Robert Padbury ◽  
Amitesh Chandra Roy ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Systemic Therapy ◽  
Lung Resection ◽  
Single Agent ◽  
Population Based ◽  
Chemotherapeutic Agents ◽  
Ageing Population ◽  
Clinical Registry ◽  
Age Range

752 Background: With improved healthcare we now face an ageing population worldwide. More patients with metastatic colorectal cancer (mCRC) will present at advanced age. Patients with mCRC now have the potential of living longer due to surgery, chemotherapeutic agents and monoclonal antibodies. Australian data (2011) indicated 1.3% of the population are aged over 90 years*. Medical oncologists are now being referred patients in their 90’s and the optimal management for this group is unknown. Methods: The population based South Australian Clinical Registry for mCRC includes all patients with metastatic CRC diagnosed since the 1st February 2006. We examined cancer characteristics, treatments administered and outcomes for patients aged > 90 years. Results: 130 patients of 4199 (3%) were aged 90 years or older. The median age was 92.1 years (range 90-104.8 years). 61% were female, 70% presented with synchronous disease. Organ involvement was as follows; 58% liver, 32% lung, 8% peritoneal and 7% bone. Primary site was: right 46%, left 28%, rectum 20%, unknown 6%. Only 4 patients had KRAS testing (all WT). 44.6% overall have had no surgery for their CRC primary. 24% of those with synchronous disease at diagnosis had resection of primary lesion and 3% had stoma formed for palliation. One patient had lung resection for metastasis. Only 4 patients received systemic therapy (age range 90-93). Lines of therapy delivered; one in 2 patients, two lines in one and 4 lines in one. Aside single agent 5FU, combination therapy (oxaliplatin/FU+/- bevacizumab) was given to two patients and cetuximab single agent in 2 (WT one, unknown one). The median survival overall was 3 months (95% CI 1.4-4.6 months). Two year survival was 10%. Conclusions: This analysis gives us some insight into the management of the very old. Female sex and right sided cancers are more frequent. Systemic therapy is rarely offered and the outlook is poor. Further research to understand whether active therapy is possible or warranted in this age group should be considered. *http://www.abs.gov.au/ausstats/[email protected]

Systemic Therapy for Metastatic Colorectal Cancer: Current Options, Current Evidence

2005 ◽  
Vol 23 (20) ◽  
pp. 4553-4560 ◽  
Author(s):  
Hanna Kelly ◽  
Richard M. Goldberg
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Response Rate ◽  
Single Agent ◽  
Chemotherapeutic Agents ◽  
Current Data ◽  
Phase Iii ◽  
Current Evidence ◽  
First Line ◽  
Improve Response Rate

Combination chemotherapy regimens including irinotecan and oxaliplatin markedly improve response rate and prolong median survival over fluorouracil with leucovorin (FU/LV), and have supplanted FU/LV as the standard systemic approach for metastatic colorectal cancer. The recent availability of five active chemotherapeutic agents has doubled the median overall survival for metastatic colorectal cancer from 10 to 20 months, and though the optimal strategy for incorporation of all drugs is still unclear, current data support the use of chemotherapy doublets in first-line rather than sequential single-agent therapy. Multidrug regimens increase both response rate and the proportion of patients able to undergo potentially curative resection. In addition, as many as 20% to 30% of patients never receive second-line chemotherapy. When used as single agents, bolus and infusional FU/LV and capecitabine are similarly effective but have differing toxicity. Chemotherapy combinations that incorporate infusion of FU are less toxic and more effective than those using bolus FU dosing. Capecitabine is under study as an alternative dosing method for use in combination regimens; however, the optimal dose has not been defined and final safety and efficacy outcomes are being addressed in ongoing phase II and III investigations. Three combinations have shown excellent first-line efficacy in phase III trials—IFL with bevacizumab, FOLFOX, and FOLFIRI—but neither of these combinations is clearly superior. Sound clinical judgment must continue to guide treatment decisions while we await data regarding the optimal combination and sequence of fluorouracil, irinotecan, oxaliplatin, bevacizumab, and cetuximab.

scholarly journals Efficacy of second-line chemotherapy after a first-line triplet in patients with metastatic colorectal cancer

2019 ◽  
Vol 26 (1) ◽  
Author(s):  
S. Bazarbashi ◽  
A. M. Hakoun ◽  
A. M. Gad ◽  
M. A. Elshenawy ◽  
A. Aljubran ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Group Performance ◽  
Chemotherapeutic Agents ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Second Line Chemotherapy ◽  
Line Therapy ◽  
Line Chemotherapy

Background Exposing patients with metastatic colorectal cancer (mcrc) to all three active chemotherapeutic agents (oxaliplatin, irinotecan, fluorouracil) has improved survival. The benefit of second-line chemotherapy after a first-line triplet is not clearly defined. We evaluated the efficacy of second-line chemotherapy in patients who had received first-line triplet therapy.Methods The medical records of patients treated on a prospective trial of first-line triplet therapy were reviewed for second-line treatment. Univariate and multivariate analyses were performed to establish factors of prognostic significance.Results Of the 53 patients who received first-line triplet therapy, 28 (53%) received second-line chemotherapy [13 men; 8 with a colon primary; mutant KRAS in 10, wild-type in 15, and unknown status in 3; Eastern Cooperative Oncology Group performance status (ps) of 1 in 16 patients, ps 2 in 3, ps 3 in 2, and unknown in 7; involved organs: liver in 17 patients, lung in 16, and peritoneum in 8]. Second-line chemotherapy consisted of xelox or folfox in 13 patients, xeliri or folfiri in 12, and single-agent irinotecan in 3. Concurrent bevacizumab was given in 16 patients (57%), and cetuximab, in 2 (7%). Median survival was 28.0 months [95% confidence interval (ci): 22.8 months to 33.2 months] for patients receiving second-line therapy and 23.0 months (95% ci: 13.2 months to 32.8 months) for those not receiving it. Best response was partial in 6 patients (21%), stable disease in 11 (39%), and progressive disease in 11 (39%). Median progression-free survival was 4.8 months (95% ci: 2.4 months to 9.6 months), and overall survival was 15 months (95% ci: 9.6 months to 20.4 months).Conclusions Second-line chemotherapy after first-line triplet therapy in mcrc is feasible and suggests efficacy comparable to that reported for second-line therapy after a doublet, regardless of the agent used.by research evidence.

scholarly journals Comparative effectiveness of chemotherapy in elderly patients with metastatic colorectal cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 463-463
Author(s):  
Sacha Satram-Hoang ◽  
Devi Ramanan ◽  
Luen F. Lee ◽  
Shui Yu ◽  
Carolina M. Reyes ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Real World ◽  
Cox Regression ◽  
Cohort Analysis ◽  
Clinical Trial Data ◽  
Chemotherapeutic Agents ◽  
Duration Of Treatment ◽  
Risk Of Death ◽  
The Mean

463 Background: The management of metastatic colorectal cancer (mCRC) has evolved considerably with advances in chemotherapeutic agents that have led to improved outcomes. Less is known about the benefits of newer agents in the real-world setting. The objective of this study was to evaluate treatment patterns and survival in older, demographically diverse mCRC patients. Methods: Using the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we conducted a retrospective cohort analysis of 5931 stage IIIB, IIIC and IV CRC patients diagnosed between 1/1/ 2000 – 12/31/2007, who were >66 years, enrolled in Medicare Parts A and B, and received first-line treatment with 5FU/LV (n=2907), CAP (capecitabine; n=963), FOLFOX (n=1856) or CAPOX (CAP + oxaliplatin; n=205). Date of last follow-up was 12/31/2009. Statistical comparisons were made between 5FU/LV vs. CAP and FOLFOX vs. CAPOX. Cox regression with backward elimination estimated the relative risk of death, adjusting for demographic and clinical factors. Results: Compared to 5FU/LV, patients treated with CAP were older (>80 years) at diagnosis (36% vs. 22%; p<.0001) and more likely female (59% vs. 53%; p=.0025), while patients receiving CAPOX were older (>80 years: 12% vs 8%; p<0.05) compared to FOLFOX. The mean time to chemotherapy initiation after diagnosis was similar between CAP and 5FU/LV (76 vs. 71 days) and between FOLFOX and CAPOX (75 vs. 70 days). The mean duration of treatment was longer for 5FU/LV (144 days) vs. CAP (122 days; p<.0001) and comparable between CAPOX (144 days) and FOLFOX (150 days; p=0.2139). The incidence of adverse events (AE) within 180 days after initiation of treatment were higher in patients treated with 5FU/LV (37%) vs. CAP (9%); p<.0001 and in FOLFOX (58%) vs. CAPOX (44%); p<0.0001. In multivariate analysis there were no significant differences in risk of death between CAP and 5FU/LV, and between CAPOX and FOLFOX ( table ). Conclusions: Overall survival was comparable between CAP and 5FU/LV and between CAPOX and FOLFOX with fewer AEs associated with CAP and CAPOX. This provides real-world confirmation of clinical trial data. [Table: see text]

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