A Prospective Multi-center Trial of Escherichia coli Extract for the Prophylactic Treatment of Patients with Chronically Recurrent Cystitis

We have assessed the efficacy and safety of Escherichia coli extract (ECE; UroVaxom (R)) which contains active immunostimulating fractions, in the prophylactic treatment of chronically recurrent cystitis. Forty-two patients with more than 2 episodes of cystitis in the proceeding 6 months were treated for 3 months with one capsule daily of ECE and observed for a further 6 months. The primary efficacy criterion was the number of episodes of recurrent cystitis during the 6 months after treatment compared to those during the 6 months before treatment. At the end of the 9-month trial, 34 patients (all women) were eligible for statistical analysis. Their mean age was 56.4 yr (range, 34-75 yr), and they had experienced recurrent urinary tract infections for 7.2 +/- 5.2 yr. The number of recurrences was significantly lower during the 6-month follow-up period than during the 6 months preceding the trial (0.35 vs. 4.26, P<0.001). During the follow-up, 28 (82.4%) patients had no recurrences and 4 (11.8%) had 1 each. In patients who relapsed, ECE alleviated cystitis symptoms, including painful voiding, frequency and urgency. There were no serious adverse events related to the study drug. Our study demonstrates the efficacy and safety of ECE in the prophylactic treatment of chronically recurrent cystitis.Ha US, 2008, INT J ANTIMICROB AG, V31, pS63, DOI 10.1016/j.ijantimicag.2007.07.018LEE SJ, 2008, KOREAN J UROL, V48, P428Krieger JN, 2002, J UROLOGY, V168, P2351, DOI 10.1097/01.ju.0000037620.30988.b2Barnett BJ, 1997, AM J MED SCI, V314, P245Nicolle LE, 1997, INFECT DIS CLIN N AM, V11, P647Baier W, 1997, ARZNEIMITTEL-FORSCH, V47, P980Lettgen B, 1996, CURR THER RES CLIN E, V57, P464AVORN J, 1994, JAMA-J AM MED ASSOC, V271, P751MAGASI P, 1994, EUR UROL, V26, P137SCHULMAN CC, 1993, J UROLOGY, V150, P917JACOBY GA, 1991, NEW ENGL J MED, V324, P601NAUCK M, 1991, INT J EXP CLIN CHEMO, V4, P1SOTOLONGO JR, 1990, J UROLOGY, V143, P979VANPHAM T, 1990, J BIOL RESP MODIF, V9, P231TAMMEN H, 1990, BRIT J UROL, V65, P6HANSSON S, 1989, BRIT MED J, V298, P856HANSSON S, 1989, BRIT MED J, V298, P853WYBRAN J, 1989, IMMUNOPHARM IMMUNOT, V11, P17BOSCH A, 1988, IMMUNOPHARM IMMUNOT, V10, P333TAMMEN H, 1988, UROLOGE, V28, P294BOTTEX C, 1988, INT J IMMUNOTHER, V4, P203FREY C, 1986, UROL INT, V41, P444HAUSER WE, 1982, AM J MED, V72, P711

Efficacy of Dendritic Cells Matured Early with OK-432 (Picibanil®), Prostaglandin E2, and Interferon-α as a Vaccine for a Hormone Refractory Prostate Cancer Cell Line

Dendritic cells (DCs) are potent antigen-presenting cells. OK432 (Picibanil®) was introduced as a potent stimulator of DC maturation in combination with prostaglandin-E2 and interferon-α. We compared the efficacy of a DC-prostate cancer vaccine using early-mature DCs stimulated with OK432, PGE2 and INF-α (OPA) with that of vaccines using other methods. On days 3 or 7 of DC culture, TNF-α (T), TNF-α and LPS (TL) or OPA were employed as maturation stimulators. DU145 cells subjected to heat stress were hybridized with mature DCs using polyethyleneglycol. T cells were sensitized by the hybrids, and their proliferative and cytokine secretion activities and cytotoxicity were measured. The yields of early-mature DCs were higher, compared to yields at the conventional maturation time (P<0.05). In the early maturation setting, the mean fusion ratios, calculated from the fraction of dual-positive cells, were 13.3%, 18.6%, and 39.9%, respectively (P=0.051) in the T only, TL, and OPA-treated groups. The function of cytotoxic T cells, which were sensitized with the hybrids containing DCs matured early with OPA, was superior to that using other methods. The antitumor effects of DC-DU145 hybrids generated with DCs subjected to early maturation with the OPA may be superior to that of the hybrids using conventional maturation methods

Analysis of Changes in the Total Lymphocyte and Eosinophil Count during Immunotherapy for Metastatic Renal Cell Carcinoma: Correlation with Response and Survival

The aims of this study were to analyze lymphocyte and eosinophil counts in consecutive peripheral blood samples taken during immunotherapy for metastatic renal cell carcinoma (mRCC) and to correlate the findings with objective response and survival. A total of 40 patients with mRCC who received immunotherapy with interleukin-2, interferon-α, and 5-fluorouracil were analyzed. Objective responses were observed in 14 patients, including 2 (5%) who showed a complete response (CR) and 12 (30%) who showed a partial response (PR). Eleven patients (27%) achieved stable disease (SD), and 15 patients (38%) had progressive disease (PD). Changes from baseline in the total lymphocyte counts were significantly higher in the responding patients (CR+PR+SD) than in the non-responding patients (PD) (p=0.017), but no difference was seen in the total eosinophil counts (p=0.275). Univariate analysis identified the Eastern Cooperative Oncology Group (ECOG) performance status (p=0.017), the presence of a primary renal tumor (p<0.001) and the peripheral lymphocyte counts at week 4 (p=0.034) as prognostic factors, but a low ECOG performance status (p=0.003) and the presence of a primary renal tumor (p=0.001) were identified as independent poor prognostic factors by multivariate analysis. This study provides further evidence that changes in blood lymphocyte counts may serve as an objective indicator of objective responses

Prostate-specific antigen response rate of sequential chemotherapy in castration-resistant prostate cancer: the results of real life practice

Prostate-specific antigen (PSA) response rate (>50% PSA decline in pretreatment PSA following chemotherapy) carries a significant survival advantage in castration-resistant prostate cancer (CRPC). We compared PSA response rates in first-, second- and third-line chemotherapy after failure of previous chemotherapy according to chemotherapeutic agents. Methods: We retrospectively evaluated the oncological outcomes and PSA response rates of 384 patients with CRPC, who were treated with chemotherapy and had histologically proven adenocarcinoma of the prostate with failure after androgen ablation therapy between 1991 and 2012, at Asan Medical Center. Results: In 384 eligible patients, the median age was 67.5 years. The median pretreatment PSA and initial Gleason scores at baseline were 92.4 ng/mL (range, 2.0 to 6,370 ng/mL) and 9 (range, 6 to 10), respectively. The time from first diagnosis of prostate cancer to CRPC was 23 months (range, 1 to 164 months). As first-line chemotherapy, 245 patients (63.8%) received estramustine, 91 (23.7%) received docetaxel, and 39 (10.2%) received mitoxantrone. The PSA response rates were 39.6%, 51.6%, and 46.2%, respectively. Of 169 patients with second-line chemotherapy, estramustine was 15 (8.9%), docetaxel was 84 (49.7%), and mitoxantrone was 52 (30.8%). PSA response rates were 57.1%, 52%, and 28.0%, respectively. Of 81 patients with third-line chemotherapy, estramustine was 18 (22.2%), docetaxel was 16 (19.8%), and mitoxantrone was 28 (34.6%). The PSA response rates were 41.2%, 53.8%, and 11.1%, respectively. Declines in serum PSA levels of at least 50% occurred more frequently after treatment with docetaxel than with other chemo-agents regardless of second-and third-line chemotherapy. Even in third-line chemothrapy, docetaxel maintained the PSA response rate, whereas the PSA response rate of other agents, including mitoxantrone, decreased in patients in whom prior therapy failed. Conclusions: Docetacel was the most effective chemotherapeutic agent in second- and third-line trials of chemotherapy in Korean CRPC patients. Although docetaxel is not used as first-line chemotherapy, and new agents are not available for therapy in CRPC patients, we can consider docetaxel a second- or third-line chemotherapy in CRPC