Numerous clinical trials of molecular targeted drugs for cancer have been conducted, with remarkable results for certain drugs and accumulation of "negative data" causing a hitch in the development plan for some other compounds. Five recent issues and problems of molecular targeted therapies were discussed critically. Drug discovery and effects against driver mutations (activating mutations) and problems: possibility for circumventing inherent and acquired resistance with the aim of achieving radical cure.
Synthetic lethality: reasonable patient selection in individualized treatment strategy. Response rate and progression-free survival improvement with or without overall survival benefit and enhancement of toxicity in bevacizumab therapy: best endpoints for the evaluation of effect of antiangiogenic therapy. Negative data on small-molecule targeted therapy, primarily vascular endothelial growth factor tyrosine kinase inhibitors: loose GO or NO-GO decision criteria for further development of new compounds in early clinical trials. Effect of immunotherapy: difficulty to verify by proof of principle study. We are faced to many questions for the development of efficient personalized therapy. Accumulation of scientific global preclinical and clinical evidences is essential to use these new therapeutic modalities for the improvement of oncologic health care.
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Mortality data from 1983-2009 were obtained from Statistics Korea. Crude rates and age-standardized rates for incidence, mortality, and prevalence; and relative survival were calculated. RESULTS In total, 192,561 cancer cases and 69,780 cancer deaths were observed during 2009, and 808,503 10-year cancer prevalent cases occurred in Korea as of 1 January 2010. The incidence rate for all cancers combined showed an annual increase of 3.3% from 1999 to 2009. CONCLUSION Stomach, liver and cervical cancers have been decreasing and thyroid, breast and colorectal cancers have been increasing at large. In particular, in 2009, colorectal cancer became the third most common cancer in females and for the first time ranked higher than stomach cancer, which had been the long-standing common cancer in Korea. While overall cancer incidence has been rapidly increasing in Korea, age-standardized cancer mortality rates have been declining since 2002, and cancer survival has been improving.
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PURPOSE To estimate the current cancer burden in Korea, cancer incidence and mortality rates were projected for the year 2012. MATERIALS AND METHODS The cancer incidence data from 1999 to 2009 were obtained from the Korea National Cancer Incidence Database, and the cancer mortality data from 1993 to 2010 were obtained from Statistics Korea. Cancer incidence in 2012 was projected by fitting a linear regression model on observed age-specific cancer incidence rates against observed years, then multiplying the projected age-specific rates by the age-specific population. For cancer mortality, a similar procedure was applied, except that a Joinpoint regression model was used to determine at which year the linear trend significantly changed. RESULTS A total of 234,727 new cancer cases and 73,313 cancer deaths are projected to occur in Korea in 2012. For all sites combined, the crude incidence rates are projected to be 465.6 and 459.7, and the age-standardized incidences to be 345.1 and 300.9 per 100,000 respectively for males and females. CONCLUSION Cancer has become an important public health concern in Korea, and as the Korean population ages, the cancer burden will continue to increase.
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Cancer Res Treat. 2012;44(1):32-36. Published online March 31, 2012
PURPOSE This study analyzed potentially functional polymorphisms in CASPASE (CASP) genes and their impact on the prognosis for Korean colorectal cancer patients. MATERIALS AND METHODS A total of 397 consecutive patients with curatively resected colorectal adenocarcinoma were enrolled in this study. Genomic DNA from these patients was extracted from fresh colorectal tissue, and the 10 polymorphisms in the CASP3, CASP6, CASP7, CASP8, CASP9, and CASP10 genes were determined using a reverse transcription polymerase chain reaction genotyping assay. RESULTS The median patient age was 63 years, and 218 (54.9%) patients had colon cancer, while 179 (45.1%) patients had rectal cancer. Univariate and multivariate survival analysis including pathologic stage, patient age, differentiation, and carcinoembryonic antigen level demonstrated that these polymorphisms were not associated with either disease-free or overall survival. CONCLUSION None of the 10 polymorphisms in the CASP genes investigated in this study was found to be an independent prognostic marker for Korean patients with curatively resected colorectal cancer.
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PURPOSE As the number of elderly patients diagnosed with non-small cell lung carcinoma (NSCLC) increases, the number of these patients receiving chemotherapy also increases.
However, limited data exists regarding the use of chemotherapy in advanced NSCLC patients who are 75 years of age or older. MATERIALS AND METHODS Between May 2002 and October 2008, data for 48 advanced NSCLC patients who were 75 years of age or older who had been treated with chemotherapy were retrospectively analyzed. RESULTS The median age of study participants at the time of first line chemotherapy was 76 years (range, 75 to 87 years) and their median Charlson comorbidity index was 2 (range, 1 to 4). Of the total 48 patients, 43 patients (90%) were treated by platinum-based doublet as a first line chemotherapy regimen. Median progression free survival for first line chemotherapy was 5.7 months (95% confidence interval [CI], 4.93 to 6.47 months) with an overall response rate of 33.3%. After first line chemotherapy, only 14 of the 48 patients (29.2%) received second line chemotherapy. The median overall survival (OS) for these patients was 8.2 months (95% CI, 4.44 to 11.96 months). Multivariate analysis results indicated that female gender and having received second-line or more chemotherapy were independent prognostic factors for increased OS for all 48 patients. Charlson Index was not a significant independent prognostic factor for survival. There were 9 treatment related deaths due to infectious causes (18.8%). CONCLUSION Patients 75 years of age or older with advanced NSCLC may obtain clinical benefit from the administration of platinum-based doublet or single agent chemotherapy.
However, oncologists must consider the aspect of safety in relation to the clinical benefits when managing this patient group.
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Therefore, to determine the appropriate dose meeting acceptable efficacy results, while minimizing toxic side effects, we treated patients with a weekly infusion of GD (weekly GD). MATERIALS AND METHODS A total of 22 patients presenting a variety of STSs were treated at Yonsei Cancer Center. All patients had metastatic or recurrent cancer and had previously received doxorubicin and ifosfamide combination chemotherapy. In all cases, gemcitabine (1,000 mg/m2) and docetaxel (35 mg/m2) were administered intravenously on days 1 and 8 of a 21-day cycle. We retrospectively reviewed the medical records of these patients. RESULTS The response rate was 4.5%, with one patient diagnosed with leiomyosarcoma having a partial response, and the disease control rate was 40.9%. The median progression-free survival (PFS) duration was 2.7 months and the PFS was correlated with the treatment response to a weekly GD. The median overall survival (OS) duration was 7.8 months and the OS was correlated with histology. There was no significant difference in OS between patients who received weekly GD as a 2nd line chemotherapy and those who received 3rd line or more. Treatment was generally well tolerated. CONCLUSION Weekly GD was well tolerated and showed moderate efficacy, indicating that this could be a reasonable option as a salvage treatment for metastatic STS.
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A Phase II Study of Gemcitabine, Vincristine, and Cisplatin (Gvp) As Second-Line Treatment for Patients with Advanced Soft Tissue Sarcoma Zhiguo Luo, Xiaowei Zhang, Wei Peng, Xianghua Wu, Huijie Wang, Hui Yu, Jialei Wang, Jianhua Chang, Xiaonan Hong Medicine.2015; 94(43): e1777. CrossRef
Emerging therapies for adult soft tissue sarcoma Stefano Radaelli, Sivia Stacchiotti, Paolo G Casali, Alessandro Gronchi Expert Review of Anticancer Therapy.2014; 14(6): 689. CrossRef
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PURPOSE The androgen receptor (AR) plays a central role in prostate cancer. Evidence from several groups indicates that epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) may enhance AR activity in prostate cancer cell lines. This study was designed to investigate the protein expression of AR, EGFR, and HER2 and to determine whether the EGFR and HER2 genes are amplified in prostate cancer tissues. MATERIALS AND METHODS The protein expression levels of AR, EGFR, and HER2 in a tissue microarray block of 66 prostate cancer samples were investigated by immunohistochemical analysis and chromogenic in situ hybridization was used to determine whether the EGFR and HER2 genes were amplified in these tissues. RESULTS The AR and EGFR proteins were expressed in 59.1% and 40.9% of prostate cancers, respectively, but their expression levels were not significantly associated with clinicopathologic factors. Of the cases in which tissues were negative for EGFR protein expression, 69.2% were positive for AR protein expression; however, AR protein expression was significantly reduced (44.4%) in tissues in which EGFR protein was expressed. HER2 expression was detected in only 1 case (1.5%). No amplification of the EGFR or HER2 genes was found in prostate cancer specimens. CONCLUSION This study was limited by small number of subjects, but it can still be inferred that the expression levels of the AR and EGFR proteins are inversely correlated in prostate cancer patients. The potential utility of EGFR and HER2 as prognostic factors or therapeutic targets warrants further study.
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PURPOSE Non-small cell lung carcinoma (NSCLC) comprises 75-85% of all lung cancers, and approximately 25% of all NSCLC patients develop brain metastasis. There are no reliable markers for predicting in which patients this metastasis will occur. DCUN1D1, also known as squamous cell carcinoma-related oncogene, is associated with tumor progression and poor outcomes in NSCLC. The objective of this study was to investigate the role of DCUN1D1 expression in cases of brain metastasis due to NSCLC. MATERIALS AND METHODS Primary tumor samples from a total of 71 cases of NSCLC, either with (n=40) or without (n=31) brain metastasis, were evaluated for DCUN1D1 expression by immunohistochemistry analysis. RESULTS DCUN1D1 expression was detected in 16 patients (23%) and tended to correlate with T classification (15% of T1-2 tumors vs. 30% of T3-4 tumors, p=0.083). DCUN1D1 expression was significantly associated with tumor stage. It was observed in none of the patients with stage I disease, 10% of those with stage II disease, and 29% with stage III disease (p=0.009). In addition, 14 of 16 DCUN1D1-positive patients resulted in brain metastasis (p=0.01). The odds ratio of brain metastasis for patients with DCUN1D1 expression was 3.112 (p=0.009). CONCLUSION DCUN1D1 expression may play a role in tumor progression and development of brain metastasis in patients with NSCLC. Evaluation of DCUN1D1 expression may provide assistance in identifying those patients who are at higher risk for brain metastasis.
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