Severe oral infection caused by Pseudomonas aeruginosa effectively treated with methylene blue-mediated photodynamic inactivation.

P. aeruginosa is a gram-negative bacterium present in nosocomial infections with high morbidity and mortality. This microorganism is frequently resistant to antibiotics, leading to clinical complications. In the present report, we described a clinical case of a patient with severe oral lesions caused by P. aeruginosa, which was refractory to antibiotics treatment and presented positive clinical outcomes after some sessions of antimicrobial photodynamic inactivation (API) mediated by methylene blue dye. We discuss the potential of API for P. aeruginosa refractory infections and possible resistance mechanisms of this microorganism to different API protocols.

A phase I study evaluating the safety and pharmacokinetics of weekly paclitaxel and carboplatin in relapsed ovarian cancer.

This phase I study sought to determine the toxicity profile, pharmacokinetics, and antitumor activity of giving carboplatin every 3 weeks and paclitaxel weekly in patients with relapsed ovarian cancer. Eligible patients with relapsed epithelial ovarian cancer and prior treatment with platinum- and paclitaxel-based therapy were treated with an escalating regimen of carboplatin (day 1) at an area under the curve (AUC) of 4-6 and 1-h infusions of paclitaxel (days 1, 8, and 15) at 50-80 mg/m(2) cycled at 3-week intervals. Pharmacokinetic studies were performed on the first day of cycles 1 and 2. All patients had a platinum-free interval of greater than 6 months from the most recent platinum treatment. A total of 77 cycles were administered to 16 patients, with a similar median number of cycles per patient at each dose level varying from 4.6 to 5.3. Febrile neutropenia and grade 4 thrombocytopenia were the dose-limiting toxicities at dose levels 3 and 4 after the third cycle, with no mucositis, nausea, vomiting, or peripheral neuropathy observed greater than grade 2. The maximum tolerated dose of carboplatin was an AUC of 5 and 80 mg/m(2) for paclitaxel. Pharmacokinetic analysis showed a marginal statistical difference with regard to reduced systemic paclitaxel concentration after cycle 2 compared with cycle 1 (P= 0.06). Of nine patients evaluable for a radiographic response, the response rate was 66.6% with a complete response of 33.3%. All five patients with nonmeasurable disease achieved a biochemical response. The combination of carboplatin given every 3 weeks at an AUC of 5 and 1-h weekly paclitaxel at 80 mg/m(2) is a feasible and reasonably well-tolerated regimen and may have significant antitumor activity in relapsed ovarian cancer patients.

Assessing interactions between mdm-2, p53, and bcl-2 as prognostic variables in muscle-invasive bladder cancer treated with neo-adjuvant chemotherapy followed by locoregional surgical treatment.

BACKGROUND: Tumor proliferation and apoptosis may be influenced by the mdm-2 gene product, which can block the antiproliferative effects of p53. bcl-2, one of a family of related genes that regulates the apoptotic pathway, exhibits a negative influence. Both individual and cooperative effects of these gene products may affect the biological behavior of primary bladder cancers and long-term outcome to standard therapy. METHODS: This study retrospectively evaluated the association with survival of mdm-2, p53, and bcl-2 expression in 59 patients with muscle-invasive, node-negative transitional cell carcinoma (TCC) treated with neo-adjuvant chemotherapy followed by locoregional surgery. Each marker was defined as an altered phenotype if >or=20% malignant cells in the primary tumor exhibited staining; normal or minimal expression was defined as <20% cells exhibiting staining. RESULTS: Altered mdm-2, p53, and bcl-2 expression was observed in 37%, 54%, and 46% of patients, respectively. In single marker analysis, altered p53 expression correlated with long-term survival (P = 0.05) but mdm-2 (P = 0.42) or bcl-2 (P = 0.17) did not. In the multiple-marker analysis, a prognostic index simultaneously assessing mdm-2, p53, and bcl-2 correlated with survival (P = 0.01). The 5-year survival for patients in which all markers were normally expressed was 54% compared with 25% in those with all three markers aberrantly expressed. Patients with aberrant expression of either one or two markers had an intermediate 5-year survival (49%). There was no association of molecular markers either alone or in combination with pathologic downstaging after neo-adjuvant chemotherapy. CONCLUSION: The cooperative effects of phenotypes determined by mdm-2, p53, and bcl-2 expression may predict survival in patients with muscle-invasive TCC of the bladder.

Phase II study of tirapazamine plus cisplatin in patients with advanced or recurrent cervical cancer.

The aim of this study was to evaluate the activity and toxicity of a tirapazamine (TPZ)/cisplatin drug combination in patients with stage IV or recurrent cervical cancer. The chemotherapy was administered for a maximum of eight cycles every 21 days. TPZ was administered intravenously at 330 mg/m(2) over a 2-h infusion, followed 1 h later by cisplatin intravenously at 75 mg/m(2) over 1 h on day 1. All patients received antiemetics including dexamethasone, ondansetron, and lorazepam. Subsequent doses were unchanged, reduced, or omitted according to observed toxicity and protocol guidelines. Response evaluation was performed every two cycles. Thirty-six patients with stage IV or recurrent cervical cancer were treated. Ninety-four percent of patients had prior radiotherapy. Two patients had prior chemotherapy. There were two complete responses and eight partial responses (27.8%). An additional 11 patients (30.6%) had stable disease as their best response. Response rate was greater in tumors outside of the previously radiated field (44.4% vs 11.1%). The median time to progression was 32.7 weeks. The most frequent grade 3 or 4 adverse events were nausea, vomiting, and fatigue, which occurred in 30.6%, 25%, and 22% of subjects, respectively. Anemia was the most frequent grade 3 or 4 hematologic toxicity at 8.3%. We conclude that the combination of cisplatin and TPZ was reasonably well tolerated in patients with recurrent or advanced cervical cancer. Further evaluation of this drug combination may be warranted.

Anthracyclines in the treatment of gynecologic malignancies.

OBJECTIVE: The purpose of this article is to present a summary of the pharmacology of anthracyclines as well as to review the results of clinical trials including patients with gynecologic malignancies treated with anthracycline-based therapy. METHODS: We performed a MEDLINE literature search of relevant clinical trials for the scope of this review that evaluated anthracycline-based therapy in gynecologic malignancies. RESULTS: Doxorubicin has established activity in carcinomas that arise in the ovary, uterine cervix, and endometrium as well as in uterine sarcomas. However, doxorubicin has structural characteristics that limit its efficacy and safety. Newer anthracyclines with distinct structure, pharmacokinetics, pharmacodynamics, and toxicity profiles have been developed to overcome the limitations of doxorubicin and to further exploit the activity of anthracyclines. Epirubicin is characterized by a structural formula that confers similar cytotoxic antitumor activity with fewer associated side effects than its analogue. Most recently, pegylated liposomal formulations, with distinct pharmacokinetic properties and a favorable toxicity profile, have shown antitumor activity as salvage therapy in ovarian cancer. Intraperitoneal mitoxantrone is also associated with activity in ovarian cancer; however, its clinical use is limited by the severity of local adverse effects. CONCLUSIONS: The role of anthracyclines in the management of advanced gynecologic malignancies is important as part of first-line therapy or as a salvage approach. Newer anthracycline agents such as epirubicin and pegylated liposomal doxorubicin are associated with a more favorable toxicity profile. Clinical trials are under way to further explore the role of newer anthracycline-based regimens as first-line or salvage treatment in gynecologic malignancies.

Endometrial stromal sarcoma: objective response to letrozole.

BACKGROUND: Low-grade endometrial stromal sarcoma is generally an indolent tumor rich in estrogen and progesterone receptors. Objective responses to hormonal therapy, most commonly with megestrol acetate, have been reported. CASE: The patient is a 51-year-old woman who presented with low-grade endometrial stromal sarcoma confined to the uterus in 1991 and was treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy. Approximately 5 years later, the patient had recurrent pelvic disease treated with radiation therapy, followed by an attempt at resection. She was treated with megestrol acetate during the period she received radiation therapy with poor tolerance. Tamoxifen was then given with no tumor response. Megestrol acetate was restarted with progression of disease in the pelvis and abdomen. Letrozole was then given at a daily dose of 2.5 mg with partial response for a duration of 9 months. CONCLUSION: Letrozole at a daily dose of 2.5 mg may be effective in low-grade endometrial stromal sarcoma with positive estrogen receptors.

Chemotherapy agents in transitional cell carcinoma: the old and the new.

Transitional cell carcinoma is a malignancy in which a number of single agents with different mechanisms of action are effective. Most older agents have limited activity, but several combinations are quite active. The most common regimens over the past 15 years were cyclophosphamide, doxorubicin, and cisplatin (CAP, CISCA); cisplatin, methotrexate, and vinblastine (CMV, MCV); and (methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC). Several new agents have been identified recently, including docetaxel, paclitaxel, gemcitabine, and ifosfamide. Combinations using these new agents now provide alternatives to the M-VAC combination that have much less toxicity and, in some instances, are used as multimodality therapy in patients with unresectable primary tumors without the degree of toxicity associated with older combinations of chemotherapy. Phase II and Phase III trials evaluating these new combinations are reviewed.

Schistosomiasis: predisposing cause for the formation of hepatic abscesses? Case report.

An adult patient with chronic schistosomiasis from an endemic area, complained about a seven day fever, along with jaundice and lumbar backache on the right side. Image exams showed multiple pyogenic liver abscesses. All the classic etiologies were discarded through clinical, radiological and laboratorial criteria. Schistosomiasis can cause pylephlebitis as a complication, along with immunesuppression, granulomatous reaction with central lobular liver necrosis and a greater risk of infection. The authors suggest that schistosomiasis in its chronic form may be the predisposing cause of multiple pyogenic liver abscesses, especially in endemic areas.