Surgery is the only curative modality for the treatment of gastric cancer. There has been no drastic improvement in the treatment of gastric cancer with chemotherapy. Clinical trials have attempted to demonstrate the benefit of the preoperative chemotherapy for gastric cancer. The benefit of the use of preoperative chemotherapy or chemoradiotherapy has been demonstrated for other solid cancers such as breast cancer, esophageal cancer and rectal cancer. Despite the rationale of the use of preoperative chemotherapy for patients with gastric cancer, the evidence of positive results with the use of preoperative chemotherapy has not been clear. Recently the British Medical Research Council Adjuvant Gastric Cancer Infusional Chemotherapy (MAGIC) study demonstrated the survival benefit of preoperative and postoperative chemotherapy. However, this study had several problems with the use of a heterogeneous population of patients, the method of surgery and the use of perioperative chemotherapy. Further studies with new drugs are warranted to determine the role of pre-operative chemotherapy for patients with gastric cancer.
Purpose: To highlight the potential factors that could predict the response rate of patients with metastatic colorectal cancer (mCRC) treated with pemetrexed combined chemotherapy after first- or second-line chemotherapy using the FOLFOX regimen. Materials and Methods: Between January 2007 and July 2014, 54 patients diagnosed and pathologically-confirmed with advanced colorectal cancer in Jiangsu Cancer Hospital and Research Institute, were enrolled. They received pemetrexed at a dose of $500mg/m^2$ by 10 minute infusion on day 1, repeated every 3 weeks. Doses were modified depending on nadir counts of blood cells. Combined chemotherapeutic agents included irinotecan, lobaplatin, carboplatin, oxaliplatin, gemcitabine, cis-platinum or bevacizumab. Multiple variables (age, sex, hemoglobin, platinum drugs combined, metastasis sites, LDH, ALP, CEA>40 ug/ml) reported earlier were selected. We used logistic regression analysis to evaluate relationships between these and tumor response. Results: On multivariable analysis, we found that age was significant in predicting the responsiveness to pemetrexed (p<0.05) combined with oxaliplatin. We did not find any other factors which were significantly associated with the response rate to chemotherapy with pemetrexed and irinotecan. Conclusions: By multivariate analysis, we found that age had significant impact on the responsiveness of pemetrexed when combined with oxaliplatin. Additional research based on genomic properties of host and tumors are needed to clarify markers for better selection of patients who could benefit from pemetrexed combined chemotherapy.
Many conventional anticancer drugs display relatively poor selectivity for neoplastic cells, in particular for solid tumors. Furthermore, expression or development of drug resistance, increased glutathione transferases as well as enhanced DNA repair decrease the efficacy of these drugs. Research efforts continue to overcome these problems by understanding these mechanisms and by developing more effective anticancer drugs. Cyclophosphamide is one of the most widely used alkylating anticancer agents. Because of its unique activation mechanism, numerous bioreversible prodrugs of phosphramide mustard, the active species of cyclophosphamide, have been investigated in an attempt to improve the therapeutic index. Solid tumors are particularly resistant to radiation and chemotherapy. There has been considerable interest in designing drugs selective for hypoxic environments prevalent in solid tumors. Much of the work had been centered on nitroheterocyclics that utilize nitroreductase enzyme systems for their activation. In this article, recent developments of anticancer prodrug design are described with a particular emphasis on exploitation of selective metabolic processes for their activation.
Objective : The Histoculture Drug Response Assay (HDRA), which measures chemosensitivity using minced tumor tissue on drug-soaked gelfoam, has been expected to overcome the limitations of in vitro chemosensitivity test in part. We analyzed interim results of HDRA in malignant gliomas to see if the test can deserve further clinical trials. Methods : Thirty-three patients with malignant gliomas were operated and their tumor samples were examined for the chemosensitivity to 10 chosen drugs by HDRA. The most sensitive chemotherapy regimen among those pre-established was chosen based on the number of sensitive drugs or total inhibition rate (IR) of the regimen. The response was evaluated by 3 month magnetic resonance image. Results : Among 13 patients who underwent total resection of the tumor, 12 showed no evidence of disease and one patient revealed progression. The response rate in 20 patients with residual tumors was 55% (3 complete and 8 partial responses). HDRA sensitivity at the cut-off value of more than one sensitive drug in the applied regimen showed a sensitivity of 100%, specificity of 60% and predictability of 70%. Another cut-off value of >80% of total IR revealed a sensitivity of 100%, specificity of 69%, and predictability of 80%. For 12 newly diagnosed glioblastoma patients, median progression-free survival of the HDRA sensitive group was 21 months, while that of the non-sensitive group was 6 months ($p$=0.07). Conclusion : HDRA for malignant glioma was inferred as a feasible method to predict the chemotherapy response. We are encouraged to launch phase 2 clinical trial with chemosensitivity on HDRA.
Systemic chemotherapy is usually regarded as the standard treatment for palliation in patients with recurrent or metastatic cancer who have failed the definite local treatment with surgery and/or radiotherapy. Recently, with the introduction of more active chemotherapeutic agents and combinations, systemic chemotherapy is being increasingly used before or after local therapy in patients with previously untreated locally advanced head and neck cancer. The most active agents for the head and neck caner are methotrexate, 5-fluorouracil (5-FU), cisplatin and bleomycin. The overall response rates to each of these four drugs are 15-30% expecially when used as first line therapy. But most of these responses are partial with a mean duration of 3-5 months. Various combinations with methotrexate, 5-FU, cisplatin, and bleomycin have been tried with overall response rates of 50-90%, and 10-20% of complete responses. The introduction of chemotherapy prior to local therapy, induction chemotherapy, has been investigated with improved survivals in patients with complete response, especially pathologic, though improvement in overall survival has not been proved yet after the induction chemotherapy. Other therapeutic modalities, such as 'Sandwich' chemotherapy between surgery and radiotherapy, concomittent chemo-radiotherapy and post local treatment adjuvant chemotherapy have been pursued with some hopeful results but these trials should be compared with prospective randomized Phase III trials. To increase the response rates and enhance the survival, important work still remains; 1. Identification of better prognostic factors, 2. Improvement in staging, 3. Development of more active and safter chemotherapeutic agents, 4. Identification of the proper sequence for the addition of chemotherapy to multimodality treatment, and 5. Testing the value of such chemotherapy in locally advanced cancer patients.
Background:In the management of patients whose primary chemotherapy has failed, very careful assessment is essential. It is important to find out as accurate a chemotherapy history as possible. Preferably it should contain the drugs which has never used before. The present report concerns the results of retreatment of pulmonary tuberculosis patients treated at National Kongju Tuberculosis Hospital. Method: A retrospective study was made through the regular follow-up of 112 smear positive cases, who were treated by four-drug regimen between July 1985 and June 1990. Four drugs were, namely prothionamide, cycloserine, para-aminosalicylic acid, and streptomycin (kanamycin or tuber-actinomycin). The duration of follow-up was over one year. Results: 1) Out of 112 cases with positive sputum AFB smear, 72 (64%) achieved the negative conversion. 2) Among the 72 patients, 85% achieved negative conversion within 3 months after treatment. 3) When the duration of patient's illness was less than 2 years, 2 to 4 years and more than 5 years, the favourable response to retreatment was 86%, 62% and 54%, respectively. 4) When the number of sensitive drugs was 4,3,2 and 1, the favourable response rate was 74%, 68%, 39% and 0%, respectively. Conclusion: The shorter the duration of patient's illness was, the larger the number of sensitive drugs was. And the larger the number of sensitive drugs was, the better the result of treatment was. Thus it is very crucial to successfully treat newly discovered patients with adequate regimens and proper case-holding.
Objective: To investigate correlations between adenosine triphosphate chemotherapy response assay (ATP-CRA) and clinical outcomes after ATP-CRA-based chemotherapy for drug selection in patients receiving intravesical chemotherapy to prevent recurrence of superficial bladder cancer after surgery. Methods: The chemosensitivities of 12 anticancer drugs were evaluated, including 5-Fu ADM, and EPI, using ATP-CRA and primary tumor cell culture in 54 patients. In addition, a further 58 patients were treated according to clinical experience. Differences in post-chemotherapeutical effects between drug sensitivity assay and experience groups were compared. Results: The evaluable rate of the test was 96.3%, the clinical effective rate was 80.8%, the sensitivity rate was 97.6% (41/42), the specificity was 20%, the total predicting accuracy was 74.3%, the positive predictive value was 83.7% (41/49), the negative predictive value was 66.7% (2/3); in the drug sensitivity test group, the clinical effective rate was 80.8%, the experience group response rate was 63.8%, with a significant difference in clinical effects between the ATP-based sensitivity and experience groups (${\chi}^2$=7.0153, P<0.01). Conclusion: ATP-CRA is a stable, accurate and potentially practical chemosensitivity test providing a predictor of chemotherapeutic response in patients with superficial bladder cancer.
Background: Chemotherapy-induced peripheral neuropathy is a major side effect of anti-cancer drugs, and our knowledge of its mechanisms is lacking. Several models for chemotherapy-induced neuropathy have been introduced. However, the outcomes of these models differ significantly among laboratories. Our object was to create a model of chemotherapy-induced neuropathy in rats with cancer. Methods: Female Sprague-Dawley rats were used. Mammary rat metastasis tumor (MRMT-1) cells were implanted subcutaneously in rats. Chemotherapy-induced peripheral neuropathy was induced by injection of cisplatin once a day for four days. The responses to mechanical and thermal stimuli were examined using von Frey filaments, acetone, and radiant heat. Results: Cisplatin (2 mg/kg/day) produced mechanical allodynia, while it did not induce cold allodynia or thermal hyperalgesia. This dose of cisplatin could work successfully against cancer. Body weight loss was not observed in cisplatin-treated rats, nor were other abnormal behaviors noted in the same rats. Conclusions: Repeated injection of intraperitoneal cisplatin induced peripheral neuropathic pain in rats. Thus, this type of rat model has broad applicability in studies related to searching for the mechanism of cisplatin-induced mechanical allodynia and agents for the treatment of neuropathic pain.
Arslan, Fatma Tas;Basbakkal, Zumrut;Kantar, Mehmet
Asian Pacific Journal of Cancer Prevention
/
v.14
no.3
/
pp.1761-1768
/
2013
This cross-sectional and descriptive study was designed to determine symptoms emerging due to chemotherapy treatment and their effects on children's quality of life. The research was carried out between February 2008 and February 2009 at the pediatric oncology clinics in four hospitals, focusing on 93 patients receiving chemotherapy. A survey form, the Pediatric Quality of Life Inventory (PedsQL 4.0) and the Memorial Symptom Assessment Scale (MSAS) were used as data collection tools. Chi-square and Student t tests were performed for data analysis. Some 51.6% of the children were aged 13-15 years old, and 51.8% were boys and 50.5% were diagnosed as having solid tumors. There were significant relations between: antimetabolite chemotherapeutics and feeling irritable and worrying (p=0.001, p=0.030); vinkoalkaloid and numbness/tingling in hands/feet (p=0.043); antracyclines and lack of energy and skin changes (p=0.021, p=0.004); and corticosteroids and lack of appetite, nausea and sadness (p=0.008, p=0.009, p=0.009). Several symptoms such as feeling sad, worrying and feeling irritable caused a significant decrease in the total domain of quality of life scores (p=0.034, p=0.012, p=0.010, respectively). Chemotherapeutic drugs can cause symptoms that can seriously affect quality of life in children.
Treatment outcomes of pediatric cancers have improved greatly with the development of improved treatment protocols, new drugs, and better supportive measures, resulting in overall survival rates greater than 70%. Survival rates are highest in acute lymphoblastic leukemia, reaching more than 90%, owing to risk-based treatment through multicenter clinical trials and protocols developed to prevent central nervous system relapse and testicular relapse in boys. New drugs including clofarabine and nelarabine are currently being evaluated in clinical trials, and other targeted agents are continuously being developed. Chimeric antigen receptor-modified T cells are now attracting interest for the treatment of recurrent or refractory disease. Stem cell transplantation is still the most effective treatment for pediatric acute myeloid leukemia (AML). However, in order to reduce treatment-related death after stem cell transplantation, there is need for improved treatments. New drugs and targeted agents are also needed for improved outcome of AML. Surgery and radiation therapy have been the mainstay for brain tumor treatment. However, chemotherapy is becoming more important for patients who are not eligible for radiotherapy owing to age. Stem cell transplant as a means of high dose chemotherapy and stem cell rescue is a new treatment modality and is often repeated for improved survival. Drugs such as temozolomide are new chemotherapeutic options. In order to achieve 100% cure in children with pediatric cancer, every possible treatment modality and effort should be considered.
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