Cancer science
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Meta Analysis Comparative Study
Which is false: oxaliplatin or fluoropyrimidine? An analysis of patients with KRAS wild-type metastatic colorectal cancer treated with first-line epidermal growth factor receptor monoclonal antibody.
This meta-analysis was performed to determine whether the addition of monoclonal antibodies (mAbs) of epidermal growth factor receptor (EGFR) to oxaliplatin-based chemotherapy treatment improves efficacy in KRAS wild-type metastatic colorectal cancer (mCRC), and whether infusional 5-fluorouracil (5-FU) and oxaliplatin is a preferred combination for EGFR mAbs. Oxaliplatin (including treatment), EGFR mAbs, first-line treatment, KRAS wild-type, and mCRC were used as key words. The PRIME, OPUS, COIN, and NORDIC VII trials were identified by two independent authors. ⋯ The addition of mAbs to oxaliplatin-based chemotherapy in patients with KRAS wild-type mCRC as first-line treatment resulted in significant improvements in PFS (HR = 0.88; 95% confidence interval (CI), 0.79-0.99; P = 0.03) and response rate (RR) (OR = 1.38; 95% CI, 1.14-1.66; P = 0.009) compared with chemotherapy alone, but the difference in OS was not significant (HR = 0.96; 95% CI, 0.85-1.08; P = 0.48). However, the differences in OS and PFS were not significant when mAbs were added to bolus 5-FU or capecitabine-based regimens compared with chemotherapy alone, whereas PFS improved with an infusional 5-FU and oxaliplatin combination (P = 0.06; PFS, HR = 0.76; 95% CI, 0.65-0.86; P = 0.0002), and even OS was marginally significant, which was consistent with the subgroup analysis of cetuximab and panitumumab. EGFR mAbs combined with oxaliplatin and an infusional 5-FU regimen was associated with significantly improved RR, PFS and OS as first-line treatment in KRAS wild-type mCRC.
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The accurate assessment of the risk of first locoregional recurrence is very important for improving the survival of patients with invasive ductal carcinoma of the breast. The present study investigated which histological factors (both well-known histological factors and factors that we have proposed) were the most capable of accurately predicting first locoregional recurrence among 1042 patients with invasive ductal carcinoma and various tumor statuses (overall, nodal status, Union Internationale Contre le Cancer pathological TNM stage, adjuvant therapy status, and adjuvant radiotherapy status) using multivariate analyses by the Cox proportional hazard regression model. The present study clearly demonstrated that the best factor for accurately predicting locoregional recurrence was grade 3 lymph vessel tumor embolus (>4 mitotic figures and >6 apoptotic figures in tumor embolus), followed by type 2 invasive ductal carcinoma (negative for fibrotic foci but positive for atypical tumor-stromal fibroblast), grade 2 lymph vessel tumor embolus (1-4 mitotic figures and >0 apoptotic figures in tumor embolus; >0 mitotic figures and 1-6 apoptotic figures in tumor embolus), primary invasive tumor cell-related factors (>19 mitotic figures, presence of tumor necrosis, presence of skin invasion) and >5 mitotic figures in metastatic carcinomas to the lymph node. Our proposed factors were superior to well-known histological factors of primary invasive tumors or clinicopathological factors for the accurate prediction of first locoregional recurrence in patients with invasive ductal carcinoma of the breast.
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The marine snail peptide ziconotide (ω-conotoxin MVIIA) is used as an analgesic in cancer patients refractory to opioids, but may induce severe adverse effects. Animal venoms represent a rich source of novel drugs, so we investigated the analgesic effects and the side-effects of spider peptide Phα1β in a model of cancer pain in mice with or without tolerance to morphine analgesia. Cancer pain was induced by the inoculation of melanoma B16-F10 cells into the hind paw of C57BL/6 mice. ⋯ Phα1β produced only mild adverse effects, whereas ω-conotoxin MVIIA induced dose-related side-effects in mice at analgesic doses (estimated toxic dose 50% of 30 pmol/site). In addition, we observed that Phα1β was capable of controlling cancer-related pain even in mice tolerant to morphine antinociception (100% of inhibition) and was able to partially restore morphine analgesia in such animals (56 ± 5% of inhibition). In this study, Phα1β was as efficacious as ω-conotoxin MVIIA in inducing analgesia in a model of cancer pain without producing severe adverse effects or losing efficacy in opioid-tolerant mice, indicating that Phα1β has a good profile for the treatment of cancer pain in patients.
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The purpose of this study was to investigate the value of post-operative radiotherapy in the treatment of pT3N0M0 breast cancer after mastectomy. We analyzed the clinical data of 1390 patients with pT1-3N0M0 breast cancer who were admitted and treated from 1998 to 2007 at the Sun Yat-sen University Cancer Center. All patients underwent mastectomy and did not receive radiotherapy. ⋯ Univariate analyses failed to identify any prognostic factors for locoregional recurrence in pT3N0 patients. Multivariate analysis showed that the T stage had no effect on locoregional recurrence. The locoregional recurrence rate in patients with pT3N0M0 breast cancer who underwent mastectomy and did not receive postoperative radiotherapy was not higher than that in patients with pT1-2N0M0 breast cancer who received the same treatment, suggesting that routine adjuvant post-operative radiotherapy should not be recommended in this patient population.
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The presence of epidermal growth factor receptor (EGFR) somatic mutations in non-small-cell lung cancer patients is associated with response to treatment with EGFR-tyrosine kinase inhibitors, such as gefitinib and erlotinib. More than 100 mutations in the kinase domain of EGFR have been identified. In particular there are many variations of deletion mutations in exon 19. ⋯ In addition, we examined the relative kinase activity of these mutants by measuring relative fluorescent intensity after immunofluorescence staining. We found that both sensitivity to EGFR-tyrosine kinase inhibitors and relative kinase activity differed among several EGFR mutations found in the same region of the kinase domain. This study underscores the importance of reporting the clinical outcome of treatment in relation to different EGFR mutations.