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Journal Issue: Vol.9, No.4 - October 2010

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Chemotherapy for Gastric Cancer: ?Who is an Asian Star??

Dr Fumio Nagashima, Ken-Ichi Fujita, Yasutsuna Sasaki

  1. Dr Fumio Nagashima
    Department of Medical Oncology, Comprehensive Cancer Center, Saitama Medical University,rn
  2. Ken-Ichi Fujita
  3. Yasutsuna Sasaki

Gastric cancer (GC) is major health problem worldwide and especially in Asia, the prognosis of unresectable or recurrent GC is poor. Recent phase III studies demonstrate survival benefit of chemotherapy for unresectable or recurrent GC. Several new agents, including S-1, capecitabine, docetaxel, paclitaxel, and irinotecan have promising effects for GC. The JCOG9912 trial revealed non-inferiority of S-1 was statistically significant. S-1 is also promising for GC in adjuvant setting. From these results, S-1 is considered to be a key-drug for treatment of GC in Japan. Based on biomarker analysis for patients with GC receiving chemotherapy, a translational research of biomarker is ongoing for patients enrolled in JCOG9912 trial. Pharmacogenetic studies provide pivotal information for cancer patients. UGT1A1*28 polymorphism has been considered to be important for predicting severe neutropenia in patients receiving irinotecan based chemotherapy. In Asian population, UGT1A1*6 is also reported to be important. We need strong collaborative network for developing new treatment strategy for GC.



The Involvement of Hypoxia-Inducible Factor- 1α in the Susceptibility to γ-rays and Chemotherapeutic Drugs of Oral Squamous Cell Carcinoma Cells

Dr Eri Sasabe, Xuan Zhou, Dechao Li, Naohisa Oku, Tetsuya Yamamoto, Tokio Osaki

  1. Dr Eri Sasabe
    Department of Oral Oncology, Kochi Medical School, Kochi University
  2. Xuan Zhou
  3. Dechao Li
  4. Naohisa Oku
  5. Tetsuya Yamamoto
  6. Tokio Osaki

The transcription factor hypoxia-inducible factor-1α (HIF-1α) is the key regulator that controls the hypoxic response of mammalian cells. The over-expression of HIF-1α has been demonstrated in many human tumors. However, the role of HIF-1α in the therapeutic efficacy of chemotherapy and radiotherapy in cancer cells is poorly understood. In this study, we investigated the influence of HIF-1α expression on the susceptibility of oral squamous cell carcinoma (OSCC) cells to chemotherapeutic drugs (cisdiamminedichloroplatinum and 5-fluorouracil) and γ-rays. Treatment with chemotherapeutic drugs and γ-rays enhanced the expression and nuclear translocation of HIF-1α, and the susceptibility of OSCC cells to the drugs and γ-rays was negatively correlated with the expression level of HIF-1α protein. The over-expression of HIF-1α induced OSCC cells to become more resistant to the anticancer agents, and down-regulation of HIF-1α expression by small interfering RNA enhanced the susceptibility of OSCC cells to them. In the HIF-1α knockdown OSCC cells, the expression of P-glycoprotein, heme oxygenase-1, manganese-superoxide dismutase and ceruloplasmin were down-regulated and the intracellular levels of chemotherapeutic drugs and reactive oxygen species were sustained at higher levels after the treatment with the anticancer agents. These results suggest that enhanced HIF-1α expression is related to the resistance of tumor cells to chemo- and radio-therapy and that HIF-1α is an effective therapeutic target for cancer treatment.


Efficacy and Tolerability of Imatinib Mesylate In Advanced Gastrointestinal Stromal Tumors

Dr Ehab Abdou, Mohamed Gaafar

  1. Dr Ehab Abdou
    Department of Radiation Oncology, Faculty of Medicine,
  2. Mohamed Gaafar

Background: IMATINIB MESYLATE is considered the standard of care for advanced or metastatic gastrointestinal stromal tumors (GIST). It acts through inhibiting the ACTIVATED KIT receptor tyrosine kinase which is critical in the pathogenesis of GIST. Methods: In our study we retrospectively evaluated the activity of Imatinib in patients with advanced or metastatic gastrointestinal stromal tumor. We assessed response rate as primary end point. Tolerance 2nd response rate, time to failure after responses and survival were the secondary end points. Results: A total of 10 patients data were collected who had received 400 mg of Imatinib daily for advanced or metastatic GIST. Seven patients (70%) had a partial response while 3 patients (30%) had stable disease. No patient had a complete response. The follow up period ranged between 5 month and 32 month with a median of 18 months. Tolerance was acceptable and manageable where mild to moderate degree (Table 2). Eight patients had edema (80%), 7 patients had diarrhea (70%), 5 patients had nausea (50%) and 4 patients had fatigue (40%). Other side effects included myalgia or musculoskeletal pain (in 40 %), dermatitis or rash (in 30%), headache (in 30%), and abdominal pain (in 30%). Gastrointestinal hemorrhage (GIT Hge) recorded for one patient (10%). One patient discontinues the treatment for non-toxicity related reason. On starting dose of Imatinib 400 mg, seven patients (70%) had partial response (PR) and 3 patients (30%) had stable disease (SD). While on re-challenging with higher dose 800 mg for progressive disease, 4 patients (40%) had PR and 3 patients (30%) had SD. None of patients had CR or PD when started either doses (table 2). All these responses were confirmed by repeated imaging at least 28 days later. The minimal response duration was 3 months while the maximum was 21 months. The response median duration was 14 months after the onset of response. Seven patients had PD and challenged with 800 mg Imatinib daily dose and successfully maintained response for minimal 2 months and maximum 14 months with a median of second response to be 10.5 months. Conclusions: In patients with an advanced unresectable or metastatic gastrointestinal stromal tumor, the objective response rate to Imatinib 400 mg is long lasting and can be repeated by higher doses i.e. 800 mg but with manageable higher rate of toxicity.


Is Adjuvant Radiotherapy Worth Giving in Surgically Resected Endometrial Cancer?

Dr Emmad E. Habib, Ezzat S. Fahmy

  1. Dr Emmad E. Habib
    MD
    Faculty of Medicine, Department of Clinical Oncology, Cairo University
  2. Ezzat S. Fahmy

Purpose: To better understand the potential risks and benefits of adjuvant radiotherapy in patients with surgically resected endometrial cancer and to identify prognostic factors. Methods & Materials: A chart review identified 64 patients with stage I and II endometrial carcinoma, treated at the Kasr El-Eini Centre of Clinical Oncology between 2002 and 2007. The median duration of followup was 27 months, and patient ages ranged from 38 to 80 years. Twenty-four patients had stage IA grade 2-3, 16 had stage IB grade 2, and 8 had stage IC grade 1 disease. Sixteen cases had stage II disease. All patients underwent radical surgery, 44 of those received post-operative radiotherapy. We determined the outcome of adjuvant treatment with postoperative pelvic radiotherapy or surgery alone, comparing loco regional control, overall survival, and treatment-related morbidity. Results: There was no statistically significant survival difference between the surgery-only and surgery-plus radiation groups in intermediate to high risk stage I and II endometrial cancer patients (p = 0.09). The 3-year overall survival rates were 79% in the irradiated group and 56% in the surgery only group, respectively. Univariate analysis of prognostic factors showed that hypertension influenced survival rate (p = 0.034). However, on multivariate analysis radiotherapy was the only independent factor affecting overall survival with an Odds Ratio (OR) of 6.9 and 95% confidence interval (CI) of 1.6-30.2. Conclusions: The survival rate was higher and the relapse rate was lower in surgically resected high risk stage I and II endometrial cancer patients receiving radiotherapy. Moreover, on multivariate analysis radiotherapy was the only independent factor affecting overall survival with an Odds Ratio (OR) of 6.9 and 95% confidence interval (CI) of 1.6-30.2. According to our data it seems that pelvic radiotherapy is of benefit for high-risk stage I and II endometrial cancer.


Recent Trends in Nanotechnology: Potential Approach for Cancer Therapy

Dr Ganesh Shesrao Bangale, B. Stephen Rathinaraj, K. S Rajesh, Gajanan Shinde, Deepak Umalkar, P.S Sona

  1. Dr Ganesh Shesrao Bangale
    M.Pharm, (PhD)
    Assistant Professor, Department of Pharmaceutics, Parul Institute of Pharmacy
  2. B. Stephen Rathinaraj
  3. K. S Rajesh
  4. Gajanan Shinde
  5. Deepak Umalkar
  6. P.S Sona

Conventional chemotherapeutic drugs are distributed non-specifically in the body where they affect both cancerous and healthy cells, resulting in dose-related side effects and inadequate drug concentrations reaching the tumour. Nonspecific drug delivery leads to significant complications that represent a serious obstacle to effective anticancer therapy. In addition, the occurrence of resistance phenomena reduces the efficacy of cancer treatment. To overcome the lack of specificity of conventional chemotherapeutic drugs, several ligand-targeted therapeutic strategies, including immunotoxins, radio-immunotherapeutics, and drug immunoconjugates, are being developed. Although these conjugated agents have shown promising efficacy compared with conventional chemotherapy drugs, limitations in their delivery efficiency still remain. Recent progress in cancer nanotechnology raises exciting opportunities for specific drug delivery. Currently developed delivery systems for anticancer agents include colloidal systems polymer implants and polymer conjugates with marketed formulation also reported.



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