Progress in the chemotherapy of metastatic cancer of the urinary tract.

Cytotoxic chemotherapy has an evolving role in the management of metastatic cancer of the bladder and urinary tract. The most responsive of these tumors are transitional cell carcinomas. Standard single agents (e.

Testicular cancer: maintaining the high cure rate.

The management of germ cell tumors has advanced dramatically, with cure rates approaching 90% to 95%. Treatment of stage I/A seminomas generally includes orchiectomy and adjuvant radiotherapy. Treatment of stage I/A nonseminomatous germ cell tumors involves orchiectomy followed by retroperitoneal lymph node dissection or active surveillance.

Surgery and adjunctive chemotherapy for invasive bladder cancer.

Invasive bladder cancer has a predilection for early, occult metastasis. Despite effective local control from radiotherapy or cystectomy, approximately 50% of the patients with clinically localized, invasive bladder cancer ultimately die of their disease. Over the past 25 years, systemic chemotherapy has been combined with definitive local treatment in an attempt to improve cure rates.

Clinical staging of prostate cancer: reproducibility and clarification of issues.

The American Joint Committee on Cancer (AJCC) staging system for prostate cancer adopted in 1992 is based on tumor-node-metastasis (TNM) designations. It has been widely accepted for use in local and advanced disease. The purpose of this study was to assess reproducibility of staging among observers and to help clarify staging issues.

Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients.

Purpose: To evaluate our long-term experience with patients treated uniformly with radical cystectomy and pelvic lymph node dissection for invasive bladder cancer and to describe the association of the primary bladder tumor stage and regional lymph node status with clinical outcomes.

Patients And Methods: All patients undergoing radical cystectomy with bilateral pelvic iliac lymphadenectomy, with the intent to cure, for transitional-cell carcinoma of the bladder between July 1971 and December 1997, with or without adjuvant radiation or chemotherapy, were evaluated. The clinical course, pathologic characteristics, and long-term clinical outcomes were evaluated in this group of patients.

Polychlorinated biphenyl (PCB) recovery from spiked organic matrix using accelerated solvent extraction (ASE) and Soxhlet extraction.

The recovery of five PCB congeners from PCB spiked organic matrices was studied using Accelerated solvent extraction (ASE) and Soxhlet extraction (SE). The chromatogram of ASE extract was found to be relatively clean and similar to that of SE extract. ASE extraction efficiency was dependent on the operation temperature and sample size loading.

Phase II trial of gemcitabine in patients with previously untreated metastatic cancer of the esophagus or gastroesophageal junction.

Background: There were approximately 12,500 cases of esophageal carcinoma diagnosed in the US in 1992 and 12,200 deaths. The impact of chemotherapy on patients with metastatic disease is marginal with a median survival of only five months. Gemcitabine (LY188011,2,2,-difluorodeoxycytidine: dFdC), an analog of cytosine arabinoside (ara-C), is a pyrimidine antimetabolite.

Advanced bladder and urothelial cancers.

After more than 40 years of use, cytotoxic chemotherapy has an evolving role in the management of advanced bladder cancer. Standard single-agent regimens, such as methotrexate, doxorubicin, vinblastine and cisplatin, have produced objective response rates of 15-25%, and combination chemotherapy causes objective regression in 50-75% of cases. Novel compounds such as ifosfamide, the taxanes and gemcitabine are now being incorporated into combination regimens, having shown activity in this disease, both in previously treated and untreated cases.

Progress in the management of metastatic bladder cancer.

Background: Inadequate survival results from single agents in the management of advanced bladder cancer have prompted several trials involving multidrug combinations to increase response rates and survival.

Methods: Since the development of the MVAC regimen (methotrexate, vinblastine, doxorubicin, and cisplatin) and the CMV regimen (cisplatin, methotrexate, and vinblastine), other regimens have been tested. We evaluate results from regimens that include cisplatin combined with gemcitabine, paclitaxel, or docetaxel, and paclitaxel combined with gemcitabine or carboplatin.

Phase II trial of gemcitabine plus cisplatin in patients with metastatic urothelial cancer.

Purpose: To assess the activity and toxicity of the combination of gemcitabine and cisplatin in the treatment of chemotherapy-naive patients with metastatic urothelial cancer.

Patients And Methods: Forty-six patients with measurable stage IV carcinoma of the urothelium were enrolled onto this trial. Gemcitabine 1,000 mg/m(2) was administered intravenously for 30 to 60 minutes on days 1, 8, and 15 of each 28-day cycle.

The clinical development of paclitaxel and the paclitaxel/carboplatin combination.

Paclitaxel and carboplatin have nonoverlapping toxicities with a broad range of clinical activity. The combination of escalating dose paclitaxel and carboplatin dosed to a fixed area under the curve (AUC) was explored in a series of phase I studies. 76 patients were treated with paclitaxel over three hours followed by a 30 min carboplatin infusion, dosed by the Calvert formula to a target AUC of 4.

Magnetic resonance imaging of response to chemotherapy in orthotopic xenografts of human bladder cancer.

Although orthotopic xenografts offer the potential for improved modeling of tumor development and response to therapy, noninvasive methods are not readily available to serially monitor tumors growing at internal sites in small rodents. In this study, magnetic resonance (MR) imaging techniques were developed using a clinical 1. 5 T whole body scanner to routinely monitor tumor growth kinetics of orthotopic UCRU-BL13 human bladder cancer xenografts after systemic chemotherapy.

Phase II study of single-agent gemcitabine in previously untreated patients with metastatic urothelial cancer.

Purpose: To determine the activity of single-agent gemcitabine in previously untreated patients with metastatic transitional cell cancer.

Methods: Forty patients with measurable disease and a Karnofsky performance status > or = 60% were enrolled at five institutions between March 1994 and October 1995. Treatment consisted of gemcitabine (1,200 mg/m2) administered weekly times three on a 4-week cycle.

Antitumor efficacy of N1,N11-diethylnorspermine on a human bladder tumor xenograft in nude athymic mice.

The spermine analogue N1,N11-diethylnorspermine (DENSPM) has been shown to induce the polyamine-acetylating enzyme spermidine/spermine N1-acetyltransferase, disrupt polyamine pool homeostasis, and inhibit tumor growth. DENSPM is currently being developed as an anti-neoplastic agent and is about to enter Phase II clinical trials. In this report, the antitumor efficacy of DENSPM was evaluated against a human transitional cell bladder BL13 carcinoma xenograft implanted orthotopically and s.

Paclitaxel and carboplatin in early phase studies: Roswell Park Cancer Institute experience in the subset of patients with lung cancer.

The combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given by 3-hour infusion followed by carboplatin infused over 30 minutes has been evaluated in a series of phase I studies and is currently being explored in a phase II study in patients with limited- and extensive-stage small cell lung cancer. Pharmacokinetic measurements were performed at all dose levels in the phase I studies, in which the use of granulocyte colony-stimulating factor in previously treated patients enabled more than twice the dose of paclitaxel to be given with low to moderate doses of carboplatin (dosed to a target area under the concentration-time curve of 4.0 mg x min x mL[-1]).

Long-term follow-up of a phase III intergroup study of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study.

Purpose: A previously reported randomized intergroup trial demonstrated that combination chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) was superior to single-agent cisplatin in patients with advanced urothelial carcinoma. We conducted a long-term analysis of patients included in the intergroup trial to examine factors associated with long-term survival.

Patients And Methods: Two-hundred fifty-five assessable patients with urothelial carcinoma were randomized to receive either single-agent cisplatin (70 mg/m2 on day 1) or combination chemotherapy with methotrexate (30 mg/m2 on days 1, 15, and 22), vinblastine (3 mg/m2 on days 2, 15, and 22), doxorubicin (30 mg/m2 on day 2), and cisplatin (70 mg/m2 on day 2).

Translational studies of glutathione in bladder cancer cell lines and human specimens.

Glutathione (GSH) levels were measured in 13 human tumor cell lines derived from carcinomas of the bladder, ovary, and colon and from melanoma and glioblastoma. High levels were found in four of five bladder cell lines. The average GSH concentration in the bladder cell lines was approximately 6-fold higher than in the non-bladder cell lines.