The changing face of chemotherapy in colorectal cancer

Waters, Justin S.; Cunningham, David

doi:10.1054/bjoc.2000.1552

Cited by 23 publications

(14 citation statements)

References 15 publications

(13 reference statements)

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“…2,4 There are currently no molecular markers established to identify patients who will most likely benefit from the CPT-11 based chemotherapy. Our goal was to identify gene expression levels of enzymes involved in critical pathways such as drug metabolism, angiogenesis and DNA repair to predict response, time to tumor progression and toxicity in patients undergoing first line CPT-11 based chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…Oncologists are currently investigating molecular markers that might help determine the patients who are more likely to respond to the different available chemotherapy regimens and who are at high risk for life-threatening toxicities. 4,5 Tailoring chemotherapy based on the genetic tumor profile would increase efficacy and decrease toxicity for patients with metastatic CRC.…”

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confidence: 99%

“…6,7 Several clinical studies, which have described CPT-11/5-FU/LV treatment as an effective chemotherapeutic regimen, have let to its establishment as a first line therapy option for patients with advanced CRC. 2,4 The most common patient side-effect from the toxicity of chemotherapy is delayed-onset diarrhea. It is induced by the detoxification of SN-38, which results in intestinal epithelial damage.…”

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confidence: 99%

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Molecular determinants of irinotecan efficacy

Vallböhmer

Iqbal

Yang

et al. 2006

Intl Journal of Cancer

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Molecular markers predicting the efficacy of CPT‐11 based chemotherapies in patients with colorectal cancer (CRC) are unknown. Therefore, we investigated whether mRNA levels of drug targets (Topoisomerase I, TS), enzymes involved in 5‐FU metabolism (DPD), in angiogenesis (EGFR, IL‐8, VEGF) and in DNA‐repair/drug detoxification (ERCC1, GST‐P1) are associated with the clinical outcome of patients with CRC treated with first‐line CPT‐11 based chemotherapy. Thirty three patients with metastatic CRC were included in the study. Intratumoral gene expression levels were assessed from paraffin‐embedded tissue samples, using laser capture microdissection and quantitative Real‐Time PCR. Complete response was observed in 1 patient, partial response in 12 patients, stable disease in 13 patients and progressive disease in 6 patients. Response was inevaluable for 1 patient. Patients with complete response or partial response were classified as responders, while patients with stable disease or progressive disease were classified as nonresponders. High intratumoral mRNA levels of EGFR, ERCC1 and GSPT‐P1 were each significantly associated with response to CPT‐11 based chemotherapy. Recursive partitioning analysis showed that mRNA levels of EGFR and ERCC1 are primarily responsible for delineating responders from nonresponders. Also, the combination of high intratumoral gene expression levels of both EGFR and ERCC1 was significantly associated with progression‐free survival. The mRNA levels of EGFR had a significant correlation with expression levels of ERCC1, GST‐P1 and VEGF. This small retrospective study suggests that gene expression levels of EGFR, ERCC1 and GST‐P1 may be useful in predicting the clinical outcome of patients with metastatic CRC treated with first‐line CPT‐11 based chemotherapy. © 2006 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

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Molecular determinants of irinotecan efficacy

Vallböhmer

Iqbal

Yang

et al. 2006

Intl Journal of Cancer

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“…However, the response rate of metastatic colorectal cancer to 5-FU is approximately 20%. Recently, aggressive treatments containing new drugs such as irinotecan (IRT) or oxaliplatin (OXT) have been utilized in place of traditional treatments solely using fluoropyrimidines [4]. IRT is a semisynthetic derivative of camptothecin that suppresses topoisomerase I.…”

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confidence: 99%

Effect of Betulinic Acid on Anticancer Drug‐Resistant Colon Cancer Cells

Jung¹,

Kim²,

Choi³

et al. 2007

Basic Clin Pharma Tox

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Primary or acquired resistance of tumours to established chemotherapeutic regimens is a major concern in oncology. Attempts to improve the survival of cancer patients largely depend on strategies to prevent tumour cell resistance. 5-Fluorouracil (5-FU)-based chemotherapy with a combination of other drugs such as irinotecan (IRT) and oxaliplatin (OXT) has been reported to be effective, even though an optimal regimen has yet to be defined due to the relatively high toxicity of the procedure. The aim of this study was to examine the effect of betulinic acid (BetA) as a chemosensitizer for anticancer drug treatment in chemoresistant colon cancer cell lines. A chemoresistant cell line to 5-fluorouracil (SNU-C5/ 5FU-R), irinotecan (SNU-C5/IRT-R) and oxaliplatin (SNU-C5/OXT-R) treatment were derived from the wild-type colon adenocarcinoma cell line (SNU-C5/WT). The effect of BetA or a combination of anticancer drugs and BetA on the multidrug resistance-related genes, caspases, Bcl-2, Bad and cell death in the SNU-C5/WT and SNU-C5/R cell lines was analysed. BetA alone was an effective chemotherapeutic drug for the SNU-C5/WT, SNU-C5/5FU-R and SNU-C5/OXT-R cells. The combination of BetA with IRT or OXT was effective against SNU-C5/5FU-R cells, and the combination of BetA with 5-fluorouracil, IRT or OXT was effective against SNU-C5/OXT-R cells. BetA induced cancer cell death by apoptosis through the mitochondrial pathway. These findings indicate that the use of BetA as a chemosensitizer may be a new strategy to enhance the efficacy of chemotherapy. However, further studies will be needed for confirmation.The incidence of colorectal cancer is 8.5% of all cancers and may be related to lifestyle, obesity, drinking, smoking and other factors. The cancer death rate due to colorectal cancer remains high [1]. Although the complete remission of colorectal cancer is possible by surgical removal, unfortunately, approximately 50% of cases eventually develop incurable metastatic disease despite adjuvant treatment [2].5-Fluorouracil (5-FU)-based chemotherapy has been used as a basic treatment protocol to prolong the survival of metastatic colorectal cancer patients and improve their quality of life [3]. However, the response rate of metastatic colorectal cancer to 5-FU is approximately 20%. Recently, aggressive treatments containing new drugs such as irinotecan (IRT) or oxaliplatin (OXT) have been utilized in place of traditional treatments solely using fluoropyrimidines [4]. IRT is a semisynthetic derivative of camptothecin that suppresses topoisomerase I. The response rate is approximately 15%, and troublesome diarrhoea may develop. Recently, to increase its efficacy, combination therapy with 5-FU and leucovorin has been used. The action mechanism of OXT is similar to that of cisplatin, carboplatin or other platinum derivatives, and within tumour cells they form a cross-link with DNA resulting in the suppression of DNA replication and RNA transcription [5]. Recently, colorectal cancer patients who failed 5-FU treatment have...

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“…New agents, such as irinotecan and oxaliplatin, have also demonstrated antitumor activity in this disease. Therefore, chemotherapy of metastatic colorectal cancer has profoundly changed in the past few years, moving from a fluoropyrimidine-modulated treatment to a more aggressive approach that includes two active agents (4).…”

Section: Introductionmentioning

confidence: 99%