Oxaliplatin combined with 5-fluorouracil, leucovorin regimen for patients with advanced colorectal cancer

Objective： To observe the efficacy and tolerability of continuously infusing 5-fluorouracil （5-FU） / folic acid combined with oxaliplatin （L-OHP/5-FU/LV regimen） as first line treatment in advanced colorectal cancer. Methods： 23 patients of advanced colorectal cancer were treated with 5-FU 500 mg/d, civ, d 1-d5, d8-d12, leucovorin 100 mg/d, iv gtt, d1, d8, folic acid tablet 60 mg/d, po, d2-d5, d9-d12, and oxaliplatin 65 mg/（m^2·d）, iv gtt, dl, d8, repeated every 21 days （one cycle）. The effect was evaluated after two cycles. Results： Complete response in 2 cases and partial response in 10 cases were observed with an overall response rate of 47.18%. Adverse effects were mainly grade 1-2, including nausea, vomiting, diarrhea, dental ulcer, peripheral neuritis and myelosuppression. Conclusion： L-OHP/5-FU/LV regimen is an effective and better tolerated alternative treatment in advanced colorectal cancer and yields promising clinical application.     

A multicenter randomized phase Ⅱ trail of Oxaliplatin in the patients with colorectal cancer

Objective： To evaluate the efficacy and safety of Oxaliplatin in the patients with colorectal cancer. Methods： In a multicenter randomized control study, a total of 144 patients were divided into four groups： Oxaliplatin （Haitong） ＋ 5-FU, CF （group A） 41 cases; 5-FU ＋ CF （group B） 41 cases; Oxaliplatin （Haitong） ＋ 5-FU, CF （group C） 31 cases; Oxaliplatin （positive drug） ＋ 5-FU ＋ CF （group D） 31 cases. Oxaliplatin combination regimen： L-OHP 130 mg/m2 i.v. infusion 2 h dl; CF 200 mg/m2 i.v. 2 h d1-d5; 5-FU 300 mg/m2 i.v. infusion 4 h d1-d5 （after CF）. 5-FU ＋ CF combination regimen： CF 200 mg/m^2 i.v. infusion 2 h d1-d5, 5-FU 300 mg/m^2 i.v. infusion 4h d1-d5 （after CF）, the schedule was repeated every 3 weeks. The total cycles were 3. Results： After three circles treatment, overall response rate of 4 groups was 24.4% （group A）, 2.4% （group B）, 25.8% （group C） and 19.4% （group D）, respectively. The response rate was significantly different between group A and group B （P 〈 0.01）, but no significant difference was observed between group C and group D （P 〉 0.05）. Conclusion： The Oxaliplatin （Haitong） for injection combination regimen is effective in the treatment of celorectal cancer.     

Current perspective: Bevacizumab in colorectal cancer – A time for reappraisal?

Bevacizumab was the first anti-angiogenic drug to be licensed in malignant disease, based on the results of a randomised trial in advanced colorectal cancer, in which the addition of bevacizumab to chemotherapy with irinotecan plus fluorouracil/leucovorin (IFL) significantly improved tumour response, progression-free survival (PFS) and overall survival (median 15.6–20.3 months, p < 0.001). A subsequent randomised trial of bevacizumab combined with fluoropyrimidine and oxaliplatin (FOLFOX or CAPOX) confirmed an improvement in PFS, but without a survival benefit, probably due to the limited duration of bevacizumab treatment. However, in the second-line setting a randomised trial of bevacizumab combined with FOLFOX showed a significant improvement in survival, similar to that observed with IFL in the first-line. A benefit from the use of bevacizumab plus chemotherapy beyond progression remains unproven but data from non-randomised trials are encouraging. In contrast, bevacizumab monotherapy has limited efficacy in advanced disease and currently there are no data to support maintenance monotherapy. Bevacizumab is recognised to cause hypertension, arterial and venous thrombosis, intestinal perforation and impairment of wound healing but can be safely used in patients undergoing surgery, particularly when the timing of surgery is controlled. At the 2009 ASCO annual meeting, the first adjuvant study to report its primary end-point, NSABP protocol C-08, failed to demonstrate an improvement in 3-year disease-free survival from the addition of bevacizumab to modified FOLFOX6 for resected stage II/III disease.Health economics have unfortunately limited the universal use of bevacizumab, but it is hoped that the future identification of predictive biomarkers may enhance the benefits and thereby improve cost-effectiveness.     

Where now for anti-EGF receptor therapies in colorectal cancer?

Current US FDA-approved monoclonal antibodies targeting the EGF receptor (EGFR) include cetuximab and panitumumab. In this article, we discuss the clinical evidence concerning the use of monoclonal antibodies targeting the EGFR in the setting of advanced colorectal cancer and the emergence of predictive molecular biomarkers. In addition, we also consider the evidence surrounding the evolution of anti-EGFR-resistance mechanisms evoked by targeted anti-EGFR therapy and potential therapeutic strategies that may counteract resistant tumor growth.     

Laparoscopic resection for colorectal cancer: is it justified?

Controversy remains regarding the appropriateness of laparoscopic methods for the curative resection of colonic neoplasms. Long-term results after minimally invasive resection must be shown to be equivalent or better than those after open resection in order to justify the new technique in the setting of cancer. This article discusses adequacy of resection and short-term results, long-term outcome data, port and abdominal wound tumors, oncologic and immunologic basic science data, and the role of laparoscopy in the treatment of rectal cancers.     

Where now for anti-EGF receptor therapies in colorectal cancer?

Current US FDA-approved monoclonal antibodies targeting the EGF receptor (EGFR) include cetuximab and panitumumab. In this article, we discuss the clinical evidence concerning the use of monoclonal antibodies targeting the EGFR in the setting of advanced colorectal cancer and the emergence of predictive molecular biomarkers. In addition, we also consider the evidence surrounding the evolution of anti-EGFR-resistance mechanisms evoked by targeted anti-EGFR therapy and potential therapeutic strategies that may counteract resistant tumor growth.     

Trocar site recurrence in laparoscopic surgery for colorectal cancer. Myth or real concern?

Despite extensive research efforts, the incidence of wound recurrence and its causes are unknown. The data reviewed in this article suggest [table: see text] that the actual rate of port-site metastasis is much lower than initially reported. Thus port-site metastasis may not be an inherent detriment of laparoscopic colectomy, but rather an unfortunate sequelae of the learning curve of the application of laparoscopy for colorectal cancer. However, the learning curve may not be easily conquered for the average general surgeon in the United States who performs six to seven colorectal resections annually. The learning curve for laparoscopic colorectal surgery has been estimated to range from 20 to 70 cases. Thus, it is intuitive that the average general surgeon in the United States may never be able to conquer these technically challenging procedures. Even in a high volume practice, some patients will be operated on within the early experience thus being placed at higher risk of this complication. Clearly, a special informed consent is needed to alert patients to the existence of this complication, the individual surgeon's experience, and the preventative measures being employed to prevent it. In the interim, the safest approach is only to offer laparoscopic colorectal resections for attempted cure of carcinoma within prospectively randomized, externally monitored, peer-reviewed trials. The final results of the large randomized prospective studies which are currently underway, and information drawn from the continuous basic science efforts, will hopefully solve these questions in the near future.     

What determines individuals’ preferences for colorectal cancer screening programmes? A discrete choice experiment

IntroductionIn many countries uptake of colorectal cancer (CRC) screening remains low.AimTo assess how procedural characteristics of CRC screening programmes determine preferences for participation and how individuals weigh these against the perceived benefits from participation in CRC screening.MethodsA discrete choice experiment was conducted among subjects in the age group of 50–75 years, including both screening-naïve subjects and participants of a CRC screening programme. Subjects were asked on their preferences for aspects of CRC screening programmes using scenarios based on pain, risk of complications, screening location, preparation, duration of procedure, screening interval and risk reduction of CRC-related death.ResultsThe response was 31% (156/500) for screening-naïve and 57% (124/210) for CRC screening participants. All aspects proved to significantly influence the respondents’ preferences. For both groups combined, respondents required an additional relative risk reduction of CRC-related death by a screening programme of 1% for every additional 10 min of duration, 5% in order to expose themselves to a small risk of complications, 10% to accept mild pain, 10% to undergo preparation with an enema, 12% to use 0.75 l of oral preparation combined with 12 h fasting and 32% to use an extensive bowel preparation. Screening intervals shorter than 10 years were significantly preferred to a 10-year screening interval.ConclusionThis study shows that especially type of bowel preparation, risk reduction of CRC related death and length of screening interval influence CRC screening preferences. Furthermore, improving awareness on CRC mortality reduction by CRC screening may increase uptake.     

Does delaying adjuvant chemotherapy after curative surgery for colorectal cancer impair survival? A meta-analysis

BackgroundIn stage III colorectal cancer (CRC), adjuvant chemotherapy (CT) is usually prescribed within two months after curative surgery. Whether or not delaying initiation of CT affects survival is still debated.Material and methodsWe performed a meta-analysis (MA) of all published studies (full papers or abstracts) comparing delayed CT with standard care. Studies were obtained from a PubMed query (keywords: CRC, adjuvant treatment, delay of CT), a review (Chau et al., 2006), cross-checking references and abstracts from the proceedings of ASCO, ASCO GI and WCGI annual meetings. We chose a cutoff delay of 8 weeks. Risk Ratios (RRs) were calculated from the recorded events (deaths, relapses). We used EasyMA software (fixed-effect model).ResultsFourteen studies (including four abstracts) were identified (17,645 patients; 5952 males, 5151 females, mean age 70 years). Of these, three could not be statistically analysed and three used another cutoff (4, 5 or 6 weeks), leaving 8 studies for main MA (13,158 patients; 3932 males, 3644 females, 5942 missing data; 5576 colon cancers, 6677 rectal, 1265 missing data). Delaying CT more than 8 weeks was associated to worse Overall Survival (OS) (RR: 1.20; 95% Confidence Interval (CI) 1.15–1.26). In the MA including all studies whatever their cutoff, longer delay was similarly associated to a worse OS but not a worse Relapse-Free Survival (RFS) (five studies).ConclusionAdjuvant chemotherapy should be started within 8 weeks after surgery. Delaying the initiation of adjuvant CT for more than 8 weeks after surgery significantly decreased OS but not RFS. This discrepancy might be due to factors not directly related to cancer (post-operative complications, social status) or to a more accurate appraisal of death.     

Has the new TNM classification for colorectal cancer improved care?

In 2009, the Union for International Cancer Control issued the seventh edition of the well-used T (tumor), N (node), and M (metastasis) classification guidelines. There has been a continual refinement of the staging for colorectal cancer since this system for assessing tumor stage was initially adopted and it has been used to guide treatment decisions for over 50 years. However, the outcome after therapy for patients with colorectal cancer is very variable, even when patients are assigned to the same TNM category. This article assesses the changes that have been made since the sixth edition and discusses whether they are, in fact, informative improvements for a practicing clinician.