To investigate oxaliplatin combined with fluorouracil-based chemoradiotherapy as preoperative treatment for locally advanced rectal cancer.
Seven hundred forty-seven patients with resectable, locally ...advanced (cT3-4 and/or cN1-2) adenocarcinoma of the mid-low rectum were randomly assigned to receive pelvic radiation (50.4 Gy in 28 daily fractions) and concomitant infused fluorouracil (225 mg/m(2)/d) either alone (arm A, n = 379) or combined with oxaliplatin (60 mg/m(2) weekly × 6; arm B, n = 368). Overall survival is the primary end point. A protocol-planned analysis of response to preoperative treatment is reported here.
Grade 3 to 4 adverse events during preoperative treatment were more frequent with oxaliplatin plus fluorouracil and radiation than with radiation and fluorouracil alone (24% v 8% of treated patients; P < .001). In arm B, 83% of the patients treated with oxaliplatin had five or more weekly administrations. Ninety-one percent, compared with 97% in the control arm, received ≥ 45 Gy (P < .001). Ninety-six percent versus 95% of patients underwent surgery with similar rates of abdominoperineal resections (20% v 18%, arm A v arm B). The rate of pathologic complete responses was 16% in both arms (odds ratio = 0.98; 95% CI, 0.66 to 1.44; P = .904). Twenty-six percent versus 29% of patients had pathologically positive lymph nodes (arm A v arm B; P = .447), 46% versus 44% had tumor infiltration beyond the muscularis propria (P = .701), and 7% versus 4% had positive circumferential resection margins (P = .239). Intra-abdominal metastases were found at surgery in 2.9% versus 0.5% of patients (arm A v arm B; P = .014).
Adding oxaliplatin to fluorouracil-based preoperative chemoradiotherapy significantly increases toxicity without affecting primary tumor response. Longer follow-up is needed to assess the impact on efficacy end points.
Metastatic colorectal cancer is one of the most common causes of cancer death worldwide, and its incidence increases with age. Treating an older RAS and BRAF wild-type patient represents a challenge ...for the medical oncologist, even more so for those patients defined as "vulnerable" and undergoing at least two lines of therapy. In this context, recent evidence supports the role of retreatment with anti-EGFR inhibitors and the use of liquid biopsy. However, frequent skin toxicity constitutes a limitation of therapy, especially in older people. Since it has been described that continuous administration of these monoclonal antibodies leads to acquired resistance to anti-EGFRs, with consequent therapeutic failure, an intermittent strategy with chemotherapy plus an anti-EGFR could help maintain the efficacy of the treatment over time, delaying the resistance and improving patients' quality of life.
In this case report, we describe the case of an older RAS and BRAF wild-type patient reporting a clinical response after first-line chemotherapy with FOLFOX + panitumumab, subsequently interrupted in the absence of disease progression. After radiological worsening and two additional lines of therapy, the reintroduction of panitumumab plus 5-fluorouracil, administered with a stop-and-go strategy, allowed the patient to benefit from the same drugs for 2 years from diagnosis, to achieve a clinical response during fourth-line treatment lasting more than 3 years, to delay resistance and to avoid unacceptable anti-EGFR skin toxicity. This patient, who died from a myocardial infarction more than 5 years after diagnosis, represents the case of a good synergy between molecular profile of disease and reintroduction of an anti-EGFR with intermittent strategy.
Purpose Given the cumulative neurotoxicity associated with oxaliplatin, a shorter duration of adjuvant therapy, if equally efficacious, would be advantageous for patients and health-care systems. ...Methods The Three or Six Colon Adjuvant trial is an open-label, phase III, multicenter, noninferiority trial randomizing patients with high-risk stage II or stage III colon cancer to receive 3 months or 6 months of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine plus oxaliplatin). Primary end-point is relapse-free survival. Results 3,759 patients were accrued from 130 Italian sites, 64% receiving FOLFOX and 36% CAPOX. Two-thirds were stage III. The median time of follow up was 62 months and 772 relapses or deaths have been observed. The hazard ratio (HR) of the 3 months versus 6 months for relapse/death was 1.14 (95% CI, 0.99 to 1.32; P for noninferiority = .514) and the CI crossed the noninferiority limit of 1.20. However, the absolute difference in 3-year RFS was 1.9% (95% CI, -0.7% to 4.4%). Counter-intuitively, while the RFS curves were similar for stage III (HR, 1.07; 95% CI, 0.91 to 1.26) and for CAPOX treated patients (HR, 0.98; 95% CI, 0.77 to 1.26), they were not for stage II and for FOLFOX treated patients, with HR of 1.41 (95% CI, 1.05 to 1.89) and 1.23 (95% CI, 1.03 to 1.46), respectively, favoring the 6 months of treatment. Conclusion The Three or Six Colon Adjuvant trial failed to formally show noninferiority of 3 versus 6 months of treatment to the predefined margin of 20% relative increase. The results depended on the adjuvant regimen and risk. For CAPOX, 3 months were as good as 6 months; for FOLFOX, 6 months added extra benefit. Counter-intuitively, the low-risk patients benefitted more than the high-risk population from the 6-month duration. The choice of regimen and duration should depend on patient characteristics and be balanced against the extra toxicity of longer therapy.
Main Recommendations
1
We recommend post-surgery endoscopic surveillance for CRC patients after intent-to-cure surgery and appropriate oncological treatment for both local and distant disease. ...Strong recommendation, low quality evidence.
2
We recommend a high quality perioperative colonoscopy before surgery for CRC or within 6 months following surgery. Strong recommendation, low quality evidence.
3
We recommend performing surveillance colonoscopy 1 year after CRC surgery. Strong recommendation, moderate quality evidence.
4
We do not recommend an intensive endoscopic surveillance strategy, e. g. annual colonoscopy, because of a lack of proven benefit. Strong recommendation, moderate quality evidence.
5
After the first surveillance colonoscopy following CRC surgery, we suggest the second colonoscopy should be performed 3 years later, and the third 5 years after the second. If additional high risk neoplastic lesions are detected, subsequent surveillance examinations at shorter intervals may be considered. Weak recommendation, low quality evidence.
6
After the initial surveillance colonoscopy, we suggest halting post-surgery endoscopic surveillance at the age of 80 years, or earlier if life-expectancy is thought to be limited by comorbidities. Weak recommendation, low quality evidence.
7
In patients with a low risk pT1 CRC treated by endoscopy with an R0 resection, we suggest the same endoscopic surveillance schedule as for any CRC. Weak recommendation, low quality evidence.
It is common practice to follow patients with colorectal cancer for some years after resection and/or adjuvant treatment.Data are lacking about how often patients should be seen,what tests should be ...performed,and what surveillance strategy has a signifi cant impact on patient outcome.Seven randomized trials have addressed this issue,but none had sufficient statistical power.Four published meta-analyses have established that overall survival is significantly improved for patients in the more intensive progra...
Colon cancer is a leading cause of cancer-related deaths worldwide. About 10% of all colon cancer patients are found to have a mutation in BRAF proto-oncogene that arise as a result of a substitution ...of amino acid valine with glutamate at position 600 (V600E). This specific mutation is also found in melanomas, but at even higher percent ? in up to 60% of patients. A particular category of drugs called BRAF inhibitors, have been developed in order to increase survival. But, while in patients with melanoma this class of drugs work well especially when combined with mitogen-activated protein kinase inhibitors, they have low efficacy in patients with metastatic colorectal cancer suggesting different mechanism of action and development of drug resistance. This review summarise recent findings aimed to highlight events in BRAF mutations in metastatic colorectal cancer.
Metastatic gastric cancer remains an incurable disease, with a relative 5-year survival rate of 7%-27%. Chemotherapy, which improves overall survival （OS） and quality of life, is the main treatment ...option. Metaanalysis has demonstrated that the best survival results obtained in earlier randomized studies were achieved with three-drug regimens containing a fluoropyrimidine, an anthracycline, and cisplatin （ECF）. Although there has been little progress in improving median OS times beyond the 9-mo plateau achievable with the standard regimens, the availability of newer agents has provided some measure of optimism. A number of new combinations incorporating docetaxel, oxaliplatin, capecitabine, and S-1 have been explored in randomized trials. Some combinations, such as epirubicin-oxaliplatincapecitabine, have been shown to be as effective as （or perhaps more effective than） ECF, and promising early data have been derived for S-1 in combination with cisplatin. One factor that might contribute to extending median OS is the advancement whenever possible to second-line cytotoxic treatments. However, the biggest hope for significant survival advances in the near future would be the combination of new targeted biological agents with existing chemotherapy first-line regimens.
Background
EOX (epirubicin, oxaliplatin, and capecitabine) is one of the standard regimens for metastatic or locally advanced gastric cancer (GC). A new combination based on fractional docetaxel ...(low-TOX) has been developed in an attempt to increase the efficacy of EOX and reduce the heavy toxicity of classical docetaxel regimens.
Methods
Overall, 169 previously untreated GC patients were randomized between EOX (
arm A
) and low-TOX (
arm B
). The primary endpoint was progression-free survival (PFS), while secondary ones were overall survival (OS), overall response rate (ORR), disease control rate (DCR), and tolerability. The study was designed to detect a 35% (80% power at a two-sided 5% significance level) PFS increase with low-TOX and an interim analysis for futility was planned after the first 127 events.
Results
At the cut-off date of interim analysis, median PFS was 6.3 months 95% confidence interval (CI) 5.0–8.1 in
arm A vs
6.3 months (95% CI 5.0–7.8) in
arm B
, without statistical difference. OS was comparable in the two arms: 12.4 in
arm A
(95% CI 9.1–19.2)
vs
11.5 months in
arm B
(95% CI 8.6–15.0). ORR was 33% and 24%, while DCR was 68% and 67%, respectively. Treatment modification (91% vs 78%,
P
= 0.017) and number of patients with CTC grade ≥ 3 adverse events (42 vs 35) were higher in arm B.
Conclusions
A triplet regimen based on the fractional dose of docetaxel achieves no improvement over EOX which remains a potential standard treatment in many patients with inoperable, locally advanced or metastatic GC.
PDF
