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Objective Clinical Responses (objective + clinical_response)
Selected AbstractsA nonreplicating adenoviral vector that contains the wild-type p53 transgene combined with chemotherapy for primary breast cancerCANCER, Issue 5 2006Safety, biologic activity of a novel gene-therapy approach, efficacy Abstract BACKGROUND. Primary systemic therapy (PST) is the standard approach to the management of patients with locally advanced breast cancer (LABC). The authors hypothesized that the intratumoral administration of a nonreplicating adenoviral vector (Ad5) that contains the human wild-type p53, AdCMV- p53, combined with chemotherapy, could increase the efficacy of PST as measured by pathologic complete response. METHODS. In a prospective, open-label, Phase II trial, 13 patients with LABC were treated with 6 3-week cycles of PST, which consisted of intratumoral injections of Ad5CMV- p53 for 2 consecutive days plus docetaxel and doxorubicin followed by surgery. p53 status was determined at baseline and was assessed immediately after the first injection (up to 48 hours). Clinical response was assessed by clinical and radiologic methods. RESULTS. The trial was terminated early, because none of the patients achieved a pathologic complete response. The median age was 56 years (range, 39,71 years), and the median tumor size was 8 cm (range, 5,11 cm). Eight patients (73%) had a p53 mutation. Serial biopsies showed an increase in p53 messenger RNA (mRNA) and p21WAF1/Cip1 mRNA. All 12 evaluable patients achieved an objective clinical response. The surgical specimens revealed scattered tumor cells with extensive tumor-infiltrate leukocytes (predominantly T-lymphocytes). At a median follow-up of 37 months (range, 30,41 months), 4 patients (30%) developed systemic recurrence, and 2 patients died. The estimate breast cancer-specific survival rate at 3 years was 84% (95% confidence interval, 65.7,100%). There was no increase in systemic toxicity. CONCLUSIONS. Ad5CMV- p53 combined with PST is safe, active, and associated with local immunomodulatory effects. The promising clinical activity of this combination deserves further investigation in randomized studies. Cancer 2006. © 2006 American Cancer Society. [source] Response of patients with advanced prostatic cancer to administration of somatostatin analog RC-160 (vapreotide) at the time of relapseTHE PROSTATE, Issue 3 2003David González Barcena Abstract BACKGROUND The aim of this study was to evaluate the effects of administration of the somatostatin analog RC-160 (vapreotide) at the time of relapse in patients with androgen independent prostate cancer. METHODS Our study included 13 patients with biopsy-proven prostate cancer, stage D3. Eight patients had been treated with a depot formulation of the agonist D-Trp-6-LH-RH, with a median remission time of 68 (range 48,102 months). Five patients were initially treated by surgical orchiectomy, but relapsed after a median time of 33 months (range 17,91 months). A new remission period with a median duration of 10 months (range 2,29 months) was induced with Ketoconazole in the orchiectomy group. At the relapse time, all the patients received 1 mg of vapreotide t.i.d., by subcutaneous route, in addition to D-Trp-6-LH-RH, or Ketoconazole in the orchiectomy group. RESULTS Eight of 13 patients demonstrated clinical improvement after 3 months of therapy with vapreotide, six showing a decrease in serum prostate specific antigen (PSA) from 234.5,±,308.5 to 68.2,±,60.5 ng/ml (mean decline 71,±,8%; P,<,0.05). Two additional patients presented a fall in serum prostatic acid phosphatase (PAP). Responding patients showed a decrease in the bone pain score from 2.62,±,0.48 to 0.37,±,0.69 and an increase in the Karnofsky performance status from 72.3,±,4.21 to 83.6,±,23.2 (P,<,0.05). In accord with the ECOG criteria, two patients had a complete response; four had partial response, and two had a stable response. Four patients did not respond and one was not evaluable. Two patients died in remission, one at 16 months due to myocardial infarction and the other at 24 months due to pneumonia. Three patients relapsed at 5, 17, and 19 months respectively. Three patients who have been followed-up for more than 3 years continued in remission (79, 45, and 45 months) respectively. Vapreotide was well tolerated, only three patients having transitory mild diarrhea. CONCLUSIONS Our results indicate that therapy with the somatostatin analog vapreotide at the time of relapse can induce objective clinical responses in some patients with prostate cancer who are refractory to androgen ablation induced by LH-RH analogs or orchiectomy. Prostate 56: 183,191, 2003. © 2003 Wiley-Liss, Inc. [source] A phase II study of gemcitabine and docetaxel therapy in patients with advanced urothelial carcinomaCANCER, Issue 9 2003Barbara J. Gitlitz M.D. Abstract BACKGROUND The objectives of the current study were to evaluate the safety and efficacy of gemcitabine plus docetaxel in patients with unresectable (Stage T4 or , N1) metastatic or locally advanced transitional cell carcinoma (TCC) of the urothelial tract. METHODS A total of 27 patients were enrolled in the current multisite study, which was performed within the University of California-Los Angeles Community Oncology Research Network. The first 10 patients in the study received 800 mg/m2 of gemcitabine intravenously on Days 1, 8, and 15 of a 28-day treatment cycle. In addition, on Day 1, the first 10 patients received 80 mg/m2 of docetaxel intravenously after completion of the gemcitabine infusion. Because of dose-limiting toxicity (neutropenia), the initial dose of docetaxel was reduced to 60 mg/m2 for the remaining patients who entered the study (n = 17 patients). RESULTS Neutropenia was the most common adverse event that occurred in patients at the Grade 3 level (in 10 of 27 patients; 37.0%) and the Grade 4 level (in 6 of 27 patients; 22.2%). There were no other adverse events at the Grade 4 toxicity level. Twenty-five of 27 patients (92.6%) completed more than 1 cycle of combination therapy and were evaluated for antitumor responses. The frequency of objective clinical responses was 33.3% (9 of 27 patients). Complete responses to therapy were observed in 2 of 27 patients (7.4%), and partial responses were observed in 7 of 27 patients (25.9%). The median duration of response was 20 weeks (range, 12+ weeks to 152 weeks). The median survival duration was 52 weeks (range, 12 weeks to 160+ weeks). Four of 27 patients (14.8%) remained alive at the time of the current data analysis. CONCLUSIONS The results of the current study suggested that combination therapy with gemcitabine and docetaxel was an effective treatment for patients with unresectable (Stage T4 or , N1) metastatic or locally advanced TCC of the urothelial tract. Gemcitabine plus docetaxel appeared to be tolerated well, and treatment-related toxicities were limited to hematologic toxicities. Because cisplatin-containing regimens are contraindicated for patients with impaired renal function, the gemcitabine plus docetaxel combination may prove to be an effective and well tolerated treatment option for these patients. Cancer 2003. © 2003 American Cancer Society. [source] Clinical applications of natural killer T cell,based immunotherapy for cancerCANCER SCIENCE, Issue 4 2008Shinichiro Motohashi Human invariant V,24 natural killer T (NKT) cells are a novel, distinct lymphocyte population, characterized by an invariant T-cell receptor V,24 chain paired with V,11. V,24 NKT cells are activated by a specific glicolipid ligand, ,-GalCer, and rapidly produce a large amount of Th1 and Th2 cytokines, thereby modulating other immune cells such as antigen-specific CD4 and CD8 T cells, NK cells, and dendritic cells. Recent studies have shown that NKT cells play pivotal regulatory roles in many immune responses, including antitumor immunity. We herein review the quantitative alteration and functional deterioration of circulating V,24 NKT cells in various cancer-bearing patients. We also summarize the recent progress in the clinical studies of NKT cell-based tumor immunotherapy. Novel immunological results including the increased peripheral blood V,24 NKT cells and IFN-producing cells after the immunotherapy were revealed. The details of the safety profile and the antitumor responses were also disclosed. Although the objective clinical responses still remain unclear, some encouraging results have emerged. Therefore, NKT cell-based immunotherapy may potentially be an effective strategy for the treatment of cancer patients. (Cancer Sci 2008; 99: 638,645) [source] | ||||||||||