Adjuvant Chemotherapy For Colorectal Cancer Research Articles

Gastrointestinal surgeons should master the adjuvant therapy of colorectal cancer

The diagnosis and treatment of colorectal cancer is one of the main diseases of gastrointestinal surgeons. It is very important to master the adjuvant chemotherapy of colorectal cancer for gastrointestinal surgeons. In recent years, with the development of a number of clinical trials and the appearance of new drugs, fluorouracil combined with oxaliplatin had been established as the standard regimen of adjuvant chemotherapy for colorectal cancer. In the current guidelines, stage III( colon cancer is the indication for adjuvant chemotherapy, while stage II( colon cancer should receive adjuvant chemotherapy is uncertain. Unlike colon cancer, adjuvant therapy of rectal cancer is not evidence-based. Especially, the indication and duration of adjuvant chemotherapy for rectal cancer after neoadjuvant chemoradiotherapy remain controversial. Adjuvant therapy of colorectal cancer still needs further investigation.

Self-directed physical activity intervention in older adults undergoing adjuvant chemotherapy for colorectal cancer: Design of a randomized controlled trial

BackgroundColorectal cancer (CRC) diagnosis and treatment can have substantial detrimental impacts on health related quality of life (HRQOL) and physical function. This is especially true for older CRC patients and is of paramount concern in chemotherapy treatment decision making; yet, few studies to date have focused on understanding and managing fatigue in older CRC patients. We present the design of a study to evaluate the feasibility and impact of a home-based, self-directed physical activity intervention on fatigue in older CRC patients receiving adjuvant chemotherapy treatment. Secondary aims pertain to intervention impact on HRQOL, physical function, and self-efficacy for managing fatigue. Methods/designMulti-site, randomized controlled trial of physical activity intervention compared to usual care in a sample of older adults undergoing adjuvant chemotherapy for CRC. Forty CRC patients will be recruited and study questionnaires/assessments will be performed at baseline, 3months, and after completion of adjuvant chemotherapy. The primary outcome is a comparison of the change in fatigue from baseline to 3months between Intervention and Control arms. We will also compare changes in engagement in physical activity, HRQOL, physical function, and self-efficacy. Exploratory analyses will compare Intervention and Control arms with regard to changes in muscle mass and a biomarker aging that is known to increase during chemotherapy (p16INK4a). DiscussionIf positive, findings from this pilot study would suggest the potential for improving the care of older persons with CRC undergoing adjuvant chemotherapy through a home-based physical activity intervention to manage fatigue, HRQOL, and physical function.Trial Registration: NCT02191969

Factors Implicated for Delay of Adjuvant Chemotherapy in Colorectal Cancer: A Meta-analysis of Observational Studies.

The survival benefit of administering adjuvant chemotherapy (AC) in colorectal cancer is well established, as is the impact of its timing. Although various factors have been associated with treatment delay, their implications remain controversial. We determined clinicopathological factors associated with delay in transition to AC via systematic review and meta-analysis. Studies assessing factors for delay in initiating AC were identified from MEDLINE, EMBASE, and Cochrane Databases. Studies were included only if relevant clinicopathological factors were adequately described and appropriate comparative groups were balanced. For each study, the odds ratio (OR) and 95 % confidence interval (CI) were estimated, regarding response to early versus delayed AC initiation. We identified 15 eligible studies involving 67,537 patients. Twelve studies were multicentre studies and three were single-center cohort studies. Meta-analysis demonstrated age >75 years [4 studies, OR = 1.44 (95 % CI 1.32-1.58)], marital status-single [3 studies, OR = 1.32 (95 % CI 1.20-1.44)], low socioeconomic status (SES) [7 studies, OR = 1.67 (95 % CI 1.32-2.12)], worse comorbidity status [5 studies, OR = 1.47 (95 % CI 1.14-1.90)], low tumour grade [7 studies, OR = 1.06 (95 % CI 1.02-1.11)], prolonged length of stay [3 studies, OR 2.37 (95 % CI 2.10-2.68)], and readmission [3 studies, OR = 3.23 (95 % CI 1.66-6.26)] were significant predictors of delayed initiation of AC. Laparoscopy compared to an open surgical approach was a significant predictor of earlier AC initiation [5 studies, OR = 0.70 (95 % CI 0.51-0.97)]. Laparoscopy is associated with earlier initiation of AC, encouraging its increased adoption. Social isolation and low SES merit consideration of approaches that counter the lack of social support and deprivation to improve cancer outcomes.

A population-based cohort study on adherence to practice guidelines for adjuvant chemotherapy in colorectal cancer.

BackgroundThe value of adjuvant chemotherapy in colorectal cancer is well studied, and guidelines have been established. Little is known about how treatment guidelines are implemented in the everyday clinical setting.MethodsThis national population-based study on nearly 34,000 patients with colorectal cancer evaluates the adherence to present clinical guidelines for adjuvant chemotherapy. Virtually all patients with colorectal cancer in Sweden during the years 2007–2012 and data from the Swedish Colorectal Cancer Registry were included.ResultsIn colon cancer stage III, adherence to national guidelines was associated with lower age, presence of multidisciplinary team (MDT) conference, low co-morbidity, and worse N stage. The MDT forum also affected whether or not high-risk stage II colon cancer patients were considered for adjuvant chemotherapy. Rectal cancer patients both in stage II and III were considered for adjuvant chemotherapy less often than colon cancer patients, but the same factors influenced the decision. Adjuvant chemotherapy was started later than eight weeks after surgery in 30% of colon cancer patients and in 38% of rectal cancer patients.ConclusionsIn Sweden, the adherence to national guidelines for adjuvant chemotherapy in colon cancer stage III is acceptable in younger and healthier patients. MDT conferences are of major importance and affect whether patients are recommended for adjuvant chemotherapy. Special consideration needs to be given to certain subgroups of patients, particularly older patients and patients with poorly differentiated tumors. There is a need to shorten the waiting time until start of chemotherapy.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-948) contains supplementary material, which is available to authorized users.

EL1 - Adjuvant Chemotherapy for Colorectal Cancer

In recent years, substantial progress has been made in the treatment of colorectal cancer, not only in the metastatic but also in the adjuvant setting. However, while worldwide consensus for the treatment of metastatic disease has been gradually established, adjuvant chemotherapy remains controversial in the following points: Should all stage II and III patients undergo adjuvant chemotherapy? Should rectal cancer be treated the same as colon cancer? Should elderly patients undergo the same treatment as younger ones? Are doublet regimens such as FOLFOX or XELOX always the best? Are target agents really useless? Are 6 months an appropriate duration of treatment? Are there any biomarkers that can predict risk of recurrence or potential benefits of adjuvant chemotherapy?The goal of postoperative adjuvant chemotherapy is to eradicate micro metastases that are present at the time of surgery, thereby increasing the cure rate. However, there are some patients without recurrence after surgery alone, and there are some patients with recurrence even though they have undergone the treatment. Personalized medicine requires consideration of both the tumor and host factors that are prognostic and predictive of benefits from treatment.In this seminar, I would like to discuss current status and possible future developments of the adjuvant chemotherapy for colorectal cancer.

Prognosis of lung cancer patients with a past history of colorectal cancer.

The prognosis in lung cancer patients with a prior history of extrapulmonary cancer is controversial. In the current multicenter joint research in Japan, we focused on the relationship between a history of colorectal cancer and its prognostic impact in patients with subsequent lung cancer. Between 2000 and 2013, we designed a retrospective multicenter study at three institutes in Japan to evaluate the prognostic factors in lung cancer patients with a previous surgery for colorectal cancer. The cohorts consisted of 123/4431 lung cancer patients with/without a previous history of surgery for colorectal cancer. The median follow-up period was 6.1 years after lung cancer surgery. The 5-year overall survival in lung cancer patients with/without colorectal cancer was not significantly different, regardless of the stage of lung cancer (overall: 71.3 versus 74.7%, P = 0.1426; Stage I lung cancer: 83.3 versus 84.8%, P = 0.3779; Stage II or more lung cancer: 47.7 versus 54.4%, P = 0.1445). Based on multivariate Cox regression analysis in 4554 lung cancer patients, a past history of colorectal cancer was not a significant prognostic factor (P = 0.5335). Among the 123 lung cancer patients with colorectal cancer, age and absence of adjuvant chemotherapy for colorectal cancer were significant prognostic factors based on multivariate analysis (P = 0.0001 and 0.0236). Furthermore, there was no difference in the overall survival of lung cancer patients according to the stage of colorectal cancer (Stage I: 74.7%; Stage II/III: 66.5%, P = 0.7239). A history of antecedent colorectal cancer did not contribute to the prognosis in patients with subsequent lung cancers.

English

Application of hemofiltercytological analysis shows its ample opportunities in assessment of polychemotherapy completeness and quality through the study of drug pathomorphosis. The objective of the study was development and studying of the clinical relevance of hemofiltercytological venous blood test as completeness and quality control of patients with colorectal cancer adjuvant chemotherapy. 35 of 39 tested cancer patients who underwent radical surgery for colorectal cancer of different localization, including cases of locally advanced stage had cancer cells in peripheral blood. Thus, the percentage of patients who had atypical cells in venous blood in postoperative period was 89.7. Adjuvant chemotherapy was offered to all 35 patients with diagnosed carcinemia and after their consent it was held in modes FOLFOX-4 and XELOX. Evaluation of anticancer drugs therapeutic action is traditionally carried out using the criteria of objective and subjective effects. The criterion of objective effect during chemotherapy of solid tumors is reduction of tumor and metastases and the criterion of subjective one is well-being of a patient. In addition, it is important to notice the highest drug resistance observed at rectum cancer, because there is a predominance of smaller stages I to II of drug pathomorphosis (9 to 7) over greater stages III-IV (7 to 1) among these cancer patients. Consequently, hemofiltercytological blood test provides a real opportunity to assess the effect of polychemotherapy and to solve the problem of chemotherapeutic treatment courses number necessary to stabilize the cancer process. Key words: Calibrated filter, hemofiltercytological blood test, carcinemia, microscreening.

Loss of special AT‐rich sequence‐binding protein 1 (SATB1) predicts poor survival in patients with colorectal cancer

Special AT-rich sequence-binding protein 1 (SATB1) is a cell type-specific matrix attachment region binding protein, functioning as a global genome organizer. This study aims to investigate the expression pattern and the prognostic value of SATB1 in colorectal cancer. Prospectively collected data were obtained and tissue microarrays were constructed from a cohort of 352 patients. SATB1 protein expression was evaluated by immunohistochemistry and scored by two independent investigators. SATB1 expression was predominantly nuclear in both normal and cancer tissues. Loss of SATB1 nuclear expression was seen in 22% of colorectal cancers compared to 1.5% of adjacent normal colorectal tissue, and was associated with worse overall survival (P=0.02) independent of age and stage of disease (HR 2.48 with 95% CI 1.31-4.70). Loss of SATB1 expression was more evident in younger patients (P=0.03), tumours with mucinous or signet ring histology (P=0.0001) and poor differentiation (P=0.005). SATB1 expression was associated with a survival advantage in patients with Dukes C tumours who received adjuvant chemotherapy. Loss of SATB1 nuclear expression correlates with poor survival and a less favourable response to adjuvant chemotherapy in colorectal cancer. The value of SATB1 in individualized colorectal cancer therapy warrants further evaluation.

The relationship between tumor and host factors and survival in patients undergoing adjuvant chemotherapy for colorectal cancer.

525 Background: The tumor microenvironment and host inflammatory responses are important determinants of outcome in colorectal cancer (CRC), however their impact on survival in patients receiving adjuvant chemotherapy remains unclear. The aim of the present study was to examine the relationship between these factors, clinicopathological characteristics and survival in patients receiving adjuvant chemotherapy for CRC. Methods: 365 patients who had undergone CRC resection at a single institution between 1997-2008 were included; 88 patients subsequently received chemotherapy. Tumor stroma percentage (TSP) and necrosis were assessed on H and E sections and graded as low or high. Local inflammatory response was assessed using the Klintrup-Mäkinen (K-M), Galon and revised Immunoscore (CD45RO+ /CD8+, and CD3+/CD8+at the invasive margin and tumor center, respectively). Systemic inflammation was assessed using modified Glasgow Prognostic Score (mGPS). Results: Patients receiving adjuvant chemotherapy were younger with a lower ASA (both P<0.05), had advanced T- and N-stage (P<0.05 and P<0.001, respectively), poor tumor differentiation (P<0.05), venous invasion (VI) (P<0.01), margin involvement, infiltrative invasive margin (both P<0.05) and high TSP (P<0.01). In those patients who received adjuvant chemotherapy, on multivariate analysis of clinicopathological factors, VI (HR 3.00, 95%CI 1.22-7.37, P=0.017), TSP (HR 3.00, 95%CI 1.26-7.12, P=0.013), K-M score (HR 5.24, 95%CI 1.21-22.68, P=0.027) and mGPS (HR 3.10 95%CI 1.47-6.55, P=0.003) were independently associated with cancer-specific survival. When the interrelationships between factors independently associated with cancer survival were examined, VI, mGPS, K-M score and TSP were independent of each other (all P>0.05). Conclusions: Compared to standard CRC pathological staging, the present results suggest that assessment of both tumor microenvironment and host inflammatory responses may have superior prognostic value compared with TNM in patients receiving adjuvant chemotherapy.

Surgeons Play a Central Role in the Utilization of Adjuvant Chemotherapy for Colorectal Cancer

Surgeons Play a Central Role in the Utilization of Adjuvant Chemotherapy for Colorectal Cancer

Helicobacter pylori and gastrointestinal symptoms in diagnostics and adjuvant chemotherapy of colorectal cancer

5-Fluorouracil (5-FU)-based chemotherapy is the mainstay of adjuvant treatment for colorectal cancer (CRC). Few studies have explored Helicobacter pylori (H. pylori)-associated gastrointestinal symptoms in the diagnosis of CRC, and the association between H. pylori infection and gastrointestinal toxicity during adjuvant chemotherapy in CRC. Seventy-nine CRC patients were randomised in a prospective clinical trial to receive 5-FU and leucovorin administered as bolus injection (Mayo regimen) or continuous infusion (simplified de Gramont regimen). H. pylori antibodies were analysed at baseline, twice monthly during treatment and after treatment up to 12 months. Thirty-seven patients (47%) were H. pylori-seronegative at baseline. There was no significant association between baseline H. pylori seropositivity (n=42; 53%) and oro-gastrointestinal toxicity during chemotherapy. The median time from symptom onset of CRC to surgery was significantly longer in patients with H. pylori infection (median time, 6 vs. 5 months; P=0.012). Functional dyspeptic symptoms at presentation significantly delayed diagnosis (median time, 7.5 vs. 5 months; P=0.035), whereas anaemia, bowel symptoms, occlusion, blood in the stool, infection and hypolactasia did not. We conclude that there is no association between H. pylori status and gastrointestinal toxicity in CRC patients during chemotherapy. Dyspeptic symptoms and presence of H. pylori may delay the diagnosis of CRC. (www.controlled-trials.com/ISRCTN98405441).

Adjuvant chemotherapy for colorectal cancer: age differences in factors influencing patients' treatment decisions

PurposeOlder colorectal cancer patients are significantly less likely than younger patients to receive guideline-recommended adjuvant chemotherapy. Previous research has indicated that patient refusal of treatment is a contributing factor. This study aimed to identify potential barriers to adjuvant chemotherapy use in older patients by examining the associations between patient age, factors influencing chemotherapy treatment decisions, and preferences for information and decision-making involvement.Patients and methodsSixty-eight patients who underwent surgery for colorectal cancer in Sydney, Australia, within the previous 24 months completed a self-administered survey.ResultsFear of dying, health status, age, quality of life, and understanding treatment procedures and effects were significantly more important to older patients (aged ≥65 years) than younger patients in deciding whether to accept chemotherapy (all P < 0.05). Reducing the risk of cancer returning and physician trust were important factors for all patients. Practical barriers such as traveling for treatment and cost were rated lowest. Older patients preferred less information and involvement in treatment decision making than younger patients. However, 60% of the older group wanted detailed information about chemotherapy, and 83% wanted some involvement in decision making. Those preferring less information and involvement still rated many factors as important in their decision making, including understanding treatment procedures and effects.ConclusionA range of factors appears to influence patients’ chemotherapy decision making, including, but not limited to, survival benefits and treatment toxicity. For older patients, balancing the risks and benefits of treatment may be made more complex by the impact of emotional motivators, greater health concerns, and conflicts between their need for understanding and their information and decision-making preferences. Through greater understanding of perceived barriers to treatment and unique motivators for treatment choice, physicians may be better able to support older patients to make informed decisions about their care.

Improving QOL and safety while reducing costs: Evidence-based adjuvant chemotherapy of colorectal cancer (CRC).

e14646 Background: The addition of oxaliplatin in adjuvant chemotherapy for stage II CRC and for elderly (≥ 70) patients with stage II or III CRC requires careful consideration. Most patients with stage II or III CRC receive oxaliplatin-based adjuvant regimens (Abrams. J Clin Oncol 2011). Mature results of the adjuvant MOSAIC and C-07 trials, however, failed to show improvement in OS or DFS among the elderly (≥ 70 years) and those with stage II CRC (Tournigand. J Clin Oncol 2012). Oxaliplatin causes neuropathy, increases the incidence and severity of febrile neutropenia, and adds substantial cost for both oxaliplatin and WBC growth factors. Methods: All chemotherapy requests submitted to Oncology Analytics for stage II and III CRC from 2009 through 2012 were analyzed. Utilization of oxaliplatin was retrospectively analyzed, with special attention to its use in those who were elderly (≥ 70 years), and for those of any age with stage II. Results: Our review showed a total of 242 adjuvant chemotherapy requests in stage II/III CRC. The majority of them, 57% (138/242), were elderly (≥ 70 years) with Stage II/III, and 24% (58/242) of any age had stage II. Thirty-four (14%) were both elderly and stage II. Overall, more than two thirds, 71% (171/242), received oxaliplatin containing regimens. More than two thirds of the elderly, regardless of stage, and more than half of all stage II patients, regardless of age, were treated with oxaliplatin containing regimens. Conclusions: The historical predominance of oxaliplatin use in the adjuvant setting, among patients over seventy years of age and/or those with stage II CRC, needs to be addressed as a priority. With mature data from the MOSAIC and C-07 trials, oncologists need to change prescribing behavior to provide less toxic therapies, thereby diminishing the incidence of neuropathy and reducing the risk of febrile neutropenia. The elimination of oxaliplatin in these subsets will also diminish costs for the Medicare population by a quarter billion dollars each year, without an adverse impact on outcome. [Table: see text]

The impact of chemotherapy-associated neutrophil/ lymphocyte counts on prognosis of adjuvant chemotherapy in colorectal cancer

BackgroundLeukocytes play an important role in cancer development. However, the impact of chemotherapy-associated neutropenia/lymphopenia on the prognosis of adjuvant chemotherapy is unknown. Here, we aimed to explore the impact of chemotherapy-associated neutrophil/lymphocyte counts on prognosis of adjuvant chemotherapy in colorectal cancer (CRC) and the risk factors for developing neutropenia/lymphopenia which showed impact on the prognosis of CRC receiving adjuvant chemotherapy.MethodsFrom February 2003 to January 2011, 243 stage II and III CRC patients receiving adjuvant chemotherapy were enrolled in this retrospective study. The associations between neutrophil/ lymphocyte counts and disease free survival (DFS)/overall survival (OS) of CRC, and the risk factors for neutropenia/lymphopenia were investigated.ResultsNo association of chemotherapy-associated neutrophil counts and CRC recurrence (AUC = 0.474, P = 0.534), death (AUC = 0.449, P = 0.249) was found by ROC analysis. However, the chemotherapy-associated lymphocyte counts could significantly affect CRC recurrence (AUC = 0.634, P = 0.001), or death(AUC = 0.607, P = 0.015), with a optimized cut-off of 0.66 × 109/L for recurrence, and 0.91 × 109/L for death, respectively. Kaplan–Meier method showed chemotherapy-associated lymphopenia <0.66 × 109/L was associated with shorter DFS (P < 0.0001), and chemotherapy-associated lymphopenia <0.91 × 109/L was associated with shorter OS (P = 0.003). Cox regression model showed chemotherapy-associated lymphopenia <0.66 × 109/L was the independent prognostic factor for DFS (HR, 3.521; 95%CI = 1.703-7.282), and chemotherapy-associated lymphopenia <0.91 × 109/L was the independent prognostic factor for OS (HR, 2.083; 95% CI = 1.103-3.936). Multivariate logistic regression showed the risk of developing chemotherapy-associated lymphopenia <0.66 × 109/L was found in those with pretreatment CEA ≥10 ng ml-1 (OR, 3.338; 95% CI = 1.523-7.315), and the risk of developing chemotherapy-associated lymphopenia <0.91 × 109/L was found in those with age >60 years (OR, 2.872; 95% CI = 1.344-6.136).ConclusionsChemotherapy-associated lymphopenia <0.66 × 109/L /0.91 × 109/L has a significant impact on the prognosis of CRC receiving adjuvant chemotherapy. Pretreatment CEA ≥10 ng ml-1 is the independent risk factor for developing lymphopenia <0.66 × 109/L, and age >60 years is the independent risk factor for developing lymphopenia <0.91 × 109/L during adjuvant chemotherapy of CRC.

Adjuvant Chemotherapy for Stage II Colon Cancer: Less Complicated Than We Thought

TO THE EDITOR: In his recent editorial, Mayer agreed with the conclusion of Tournigand et al that there is no benefit for the inclusion of oxaliplatin in adjuvant chemotherapy regimens for patients with standard or indeed high-risk stage II colon cancer. Mayer then posed the question as to whether these patients, with a generally favorable prognosis, merit any adjuvant treatment at all. The virtues of prolonged clinical trial follow-up to provide mature survival data were extolled, but it surprised us greatly that no mention was made of Quasar (Quick and Simple and Reliable) 1 (A UKCCR[United Kingdom Coordinating Committee on Cancer Research] Study of Adjuvant Chemotherapy for Colorectal Cancer), the only trial in this field to show a survival benefit for patients with stage II colon cancer. In the Quasar 1 study, 2,291 patients with colon cancer were randomly assigned to receive chemotherapy with fluorouracil and leucovorin or to undergo observation. After a median follow-up of 5.5 years, the trial demonstrated that although the absolute improvements are small, the relative risk of death that was observed translates into a significant absolute improvement in survival of 3.6% (95% CI, 1.0 to 6.0; P .04). This is by far the largest and therefore the most informative trial of chemotherapy ever undertaken for this disease, and it is the only trial to show a significant survival benefit. The fluorouracil-based chemotherapy was well tolerated, and we believe that these results are sufficient to mandate an informed discussion with all patients with stage II colon cancer so that at least the offer of treatment might be made. Furthermore, we have worked with colleagues from the National Surgical Adjuvant Breast and Bowel Project, the Cleveland Clinic, and Genomic Health to develop a polymerase chain reaction– based prognostic gene signature that has now been validated in more than 5,000 patients. This can be used to define the risk of recurrence with greater precision than conventionally accepted high-risk criteria, and therefore can inform and influence the outcome of the physicianpatient consultation. We believe that there are data and validated tools that support rational and informed decision making on the utility of adjuvant fluorouracil-based therapy for patients with stage II colon cancer, and that matters are not necessarily as nihilistic as Mayer implies.

Therapeutic implications of DNA mismatch repair in adjuvant colorectal cancer chemotherapy

SUMMARY Microsatellite instability (MSI) is a molecular marker of defective DNA mismatch repair (MMR) and constitutes an important oncogenic molecular pathway in colorectal cancer that is present in approximately 12–15% of all colorectal malignant tumors. Defective MMR status in colorectal cancer occurs as a result of germline mutations in MMR genes (less than one third of cases) or, more commonly, from somatic hypermethylation of the MLH1 promoter (more than two thirds). MMR deficiency accelerates colorectal oncogenesis by accumulation of secondary mutations in specific target genes. Patients with defective MMR tumors have distinct clinicopathologic characteristics and have been associated with a better stage-adjusted prognosis than patients with proficient MMR tumors. MMR deficiency may predict tumor chemoresistance to adjuvant 5-fluorouracil treatment. Preliminary clinical data suggested that adding oxaliplatin to 5-fluorouracil could restore the benefit of adjuvant chemotherapy in MSI patients. Further studies are needed to clarify the differential chemosensitivity of MSI patients depending on the mechanism of MMR deficiency and the adjuvant chemotherapeutic regimen used.

Liver metastasectomy after neo adjuvant chemotherapy in colorectal cancer: A word of caution

Liver metastasectomy after neo adjuvant chemotherapy in colorectal cancer: A word of caution

Effects of Tegafur or 5-fluorouracil combined with oxaliplatin in adjuvant chemotherapy of colorectal cancer

Effects of Tegafur or 5-fluorouracil combined with oxaliplatin in adjuvant chemotherapy of colorectal cancer

Adjuvant Chemotherapy for Colorectal Cancer–Timing is Everything

Adjuvant Chemotherapy for Colorectal Cancer–Timing is Everything

542P - Down-Regulation of γ-Glutamyl Hydrolase Gene Expression in Tumor Tissues is Associated with Response to Oral Uracil and Tegafur/Leucovorin Chemotherapy in Patients with Colorectal Cancer

ABSTRACT Background 5-Flurouracil (5-FU)/leucovorin (LV) and oral uracil and tegafur (UFT)/LV are widely used as standard adjuvant chemotherapy for colorectal cancer (CRC). We previously reported that right-sided tumors with high thymidine phosphorylase (TP) gene expression on pre-chemotherapy tumor biopsy are associated with a response to UFT/LV chemotherapy in patients with CRC. In the present study, we examined the relation between chemotherapy-induced gene expression changes (post-chemotherapy/pre-chemotherapy gene expression ratio) in CRC tissues and the efficacy of UFT/LV treatment. Material and methods The subjects were 73 patients with CRC who were scheduled to undergo surgery. UFT (300 mg/m2/day) and LV (75 mg/day) were administered for 2 weeks before surgery. We assessed pathological response based on the extent of residual cancer cells and granulation tissue. The mRNA expressions of 6 pyrimidine-related enzymes and 8 reduced folate-related enzymes were quantitatively evaluated using a RT-PCR assay in paired samples of pre-chemotherapy tumor-biopsy specimens and post-chemotherapy resected-tumor specimens. Results Pathological responses were observed in 19.2% (14/73) of the patients. Gene expression of γ-glutamyl hydrolase (GGH) was generally down-regulated after chemotherapy, and the extent of GGH down-regulation among the responders was significantly greater than that among the non-responders, with the least p value of 0.0009 among the genes studied. The extent of GGH down-regulation among right-sided tumors with high sensitivity to UFT/LV chemotherapy was significantly greater than that among left-sided tumors (p = 0.0135). Moreover, on combined analysis of tumor site and sex, the extent of GGH down-regulation among left-sided tumors in men that showed low sensitivity to UFT/LV chemotherapy was significantly smaller than that among other tumors (p = 0.0018). Conclusion Down-regulation of GGH gene expression in primary CRC tissues after UFT/LV chemotherapy is associated with a response to chemotherapy in patients with CRC. Disclosure H. Nagase: He is an employee of Taiho Pharmaceutical Co. J. Uchida: He is an employee of Taiho Pharmaceutical Co. All other authors have declared no conflicts of interest.