Adjuvant chemotherapy of bladder cancer.
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Antineoplastic Agents↗
Biomedical subjects
F M Torti
Publications and source records attributed to F M Torti.
Failure of adjuvant chemotherapy in testicular cancer.
Two cases of failure of adjuvant chemotherapy after retroperitoneal lymph node dissection of Stage II nonseminomatous germ cell tumors are described. In both cases, initial surgical resection was complete, and two cycles of chemotherapy with cisplatin, vinblastine, and bleomycin were administered in an appropriate dose and schedule. Although one patient remains without evidence of disease 12 months after initiation of salvage chemotherapy with cisplatin, etoposide, and bleomycin, the other patient died of progressive disease despite intensive treatment with cisplatin and etoposide. Adjuvant therapy for Stage II germ cell tumors is not conventional treatment, and should be applied only in investigative settings where the long term effects and toxicity can be monitored, and does not reduce the need for frequent and thorough follow-up of treated patients.
Adult↗
Superficial bladder cancer. Risk of recurrence and potential role for interferon therapy.
Superficial bladder tumors--cancer in situ (CIS) and papillary transitional carcinoma of the bladder--are the most frequent presentations of bladder cancer, the second most common disease of the urethelial tract. These superficial tumors demonstrate a tendency to recur, either at the same stage and grade or as deeply invasive tumors. To some extent, the likelihood of tumor recurrence can be predicted, based on certain risk factors. Furthermore, the probability of recurrence can be altered through appropriate clinical interventions. A review of the literature, much of which is preliminary, suggests that interferon therapy for bladder cancer may modify the biologic behavior of this disease and provide clinical benefit for some patients.
Administration, Intravesical↗
Approaches to the treatment of bladder cancer at Stanford.
The treatment of bladder cancer is one of the most active areas of clinical cancer research. The use of new classes of intravesical agents, such as the interferons, and analogues of effective intravesical chemotherapies, such as epirubicin, the 4-epimer of doxorubicin, show promise of controlling the sequela of this common urologic problem. In metastatic transitional cell carcinoma, the CMV regimen holds promise of palliation for many and or long-term remission for some patients with advanced bladder cancer.
Administration, Intravesical↗
Superficial bladder cancer: the primacy of grade in the development of invasive disease.
Tumor characteristics thought to predict for development of deep muscle invasion after resection of superficial bladder cancer were retrospectively analyzed in 252 patients with transitional cell carcinoma of the bladder at Stanford University Medical Center. Stage 0 patients accounted for 190 of the patient population (75.5%), while stage A and B1 comprised 51 (20%) and 11 (4.5%), respectively. The median follow-up time was 62 months. Forty-three patients subsequently developed deep muscle invasion; these included 24 (12.6%), 14 (27.5%), and 5 (45.5%) of stage 0, A, and B1 patients (P = .002), or 15 (10%), 15 (9%), and 13 (33%) of grade 1, 2, and 3 tumors (P = .001), respectively. When analyzed by univariate logistic regression, grade (P = .0001) and stage (P = .0118) were significant predictors for invasive disease. Site of tumor and number of tumors at presentation were not significant factors for invasion deep into the bladder wall. When multiple logistic regression was performed, only grade remained as a significant tumor variable to predict for invasive disease (P less than .0091). Risk of invasive disease did not appear to increase with increasing number of recurrences, remaining at approximately an 11% invasion rate through 12 recurrences. In this analysis, grade was the most significant tumor variable in superficial bladder cancer predicting for the development of invasive carcinoma. Future clinical trials for definitive or adjuvant therapy of this disease must stratify for this variable.
Adult↗
Esorubicin in refractory metastatic carcinoma of the breast: a Northern California Oncology Group Study.
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Adult↗
Primary osteogenic sarcoma of the bladder. Case report and review of the literature.
Primary osteogenic sarcoma of the bladder is an extremely rare disease. Fewer than 30 cases of tumors of the bladder containing bone or cartilage have been reported. Only 14 cases of well-documented primary osteogenic sarcoma of the bladder appear in the world's literature. The authors describe the first detailed description of such a patient treated with radiotherapy and chemotherapy as well as provide a review of this rare and interesting entity.
Humans↗
Hormonal risk factors in testicular cancer. A case-control study.
The authors interviewed 273 northern California testicular cancer cases aged 40 and under diagnosed between 1976 and 1981, their mothers, and matched peer controls and their mothers on prenatal hormone exposure and other variables. Included was a population-based substudy (1979-1981) of all interviewable cases reported to the San Francisco Bay Area Surveillance, Epidemiology, and End Results registry. They found odds ratios (OR) of from 8.3 (sons' report) to 4.5 (mothers' report) associated with cryptorchidism, but found no association with mothers' hormone exposure or diethylstilbestrol exposure in pregnancy. They also found a significant association with lower age at puberty (OR = 2.0); a marginally significant association with mothers' breast cancer (OR = 2.9, p = 0.054); and a significant protective effect of reported mononucleosis (OR = 0.6). These associations remained strong in the population-based substudy. When cases were divided by histology, strong and specific associations of earlier puberty (OR = 2.3) and mothers' breast cancer (OR = 4.4) with nonseminomatous cancer, and of reported mononucleosis (OR = 0.3) with seminomatous cancer, were found. These observations suggest that 1) prenatal exogenous hormone exposure does not account for a significant fraction of testicular cancer, 2) a cluster of "breast-cancer-like" risk factors are associated with nonseminomas, and 3) there is some genetic risk of nonseminomas.
Adult↗
Hormonal control of adipogenesis.
The concept that hormonal substances can alter the expression of entire developmental programs is in itself not particularly new. The ability to define conditions under which a specific hormone can precociously activate the differentiation of a well-defined population of cells and under which another hormone can both block and reverse such a developmental progression, however, provides a major step forward toward unraveling the biochemical events that define the transition from a committed precursor to a fully differentiated cell. Further analysis of the molecular events initiated by glucocorticoids and TNF should provide insights into the control of adipogenesis and may generate a foundation for understanding the mechanisms by which other cells enter a particular differentiative lineage. In a more applied sense, such knowledge may also provide a rational approach to controlling metabolic disease syndromes related to adipogenesis gone awry such as obesity-associated diabetes and cachexia.
Adipose Tissue↗
Possible risk of invasive pulmonary aspergillosis with marijuana use during chemotherapy for small cell lung cancer.
Bacterial and fungal contaminants have been identified in marijuana samples and thus are a potential risk factor in the immunocompromised patient using it as an antiemetic. We describe the development of an invasive pulmonary aspergillosis in a patient using illicitly obtained marijuana as an antiemetic during combination antitumor therapy for small cell lung cancer. Although this patient had multiple risk factors implicated in the development of invasive pulmonary aspergillosis, the infectious potential of inhaled marijuana must be recognized. Further study of this potential health risk in needed.
Antiemetics↗
Cardiotoxicity of epirubicin and doxorubicin: assessment by endomyocardial biopsy.
Forty-two evaluable endomyocardial biopsies were obtained from 29 patients treated with epirubicin, the 4'-epimer of doxorubicin in cumulative doses ranging from 147 mg/m2 to 888 mg/m2. In this study of the Northern California Oncology Group, myofibrillar loss and sarcoplasmic vacuolization were identified and shown to be identical to those previously described for doxorubicin. However, when these biopsies were compared to 119 biopsies obtained from 98 patients treated with doxorubicin, milligram for milligram, epirubicin caused less endomyocardial injury than doxorubicin (P = 0.0013). Age, sex, type of primary malignancy, prior cardiac disease, and hypertension did not influence the degree of histologically demonstrated anthracycline injury induced by epirubicin.
Adult↗
Superficial carcinoma of the bladder: natural history and the role of interferons.
Superficial transitional cell carcinoma of the bladder is a chronic disease. Patients face a lifetime with the potential for further neoplastic manifestations--the recurrence of either superficial or deeply invasive tumor. To some extent, the likelihood of disease recurrence can be predicted. Further, certain clinical interventions can alter the probability of tumor recurrence. This paper focuses on those patient and tumor characteristics that predict for the propensity to develop recurrent disease, with emphasis on the potential of the interferons to both treat this disease and to modify its natural history.
Carcinoma in Situ↗
Hormonal control of developmentally regulated adipose genes.
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Adipose Tissue↗
A randomized study of doxorubicin versus doxorubicin plus cisplatin in endocrine-unresponsive metastatic prostatic carcinoma.
Thirty-seven patients with hormonally refractory prostatic carcinoma entered a randomized trial comparing doxorubicin and doxorubicin plus cisplatin. All patients had failed prior hormonal treatment. Mean Karnofsky performance status (76% doxorubicin versus 75% combination), percent of patients with prior palliative irradiation (40% doxorubicin versus 35% combination), and hemoglobin levels of less than or equal to 12 g/dl (30% doxorubicin versus 24% combination) were roughly equivalent in the two treatment groups. More patients treated with doxorubicin than the combination treatment had an elevated acid phosphatase level at study entry (90% versus 65%). Measurable bidimensional tumors were present in 13 patients in 16 sites in the doxorubicin arm and in 10 patients in 11 sites in the combination arm. Partial responses were seen in 1 of 13 patients in the doxorubicin arm and 2 (20%) of 10 patients in the combination arm. Improvement in Karnofsky performance status of 20% or greater was rarely observed with either treatment (7% doxorubicin versus 8% combination). Acid phosphatase levels normalized or improved by 50% in 39% of patients who received doxorubicin and 27% of patients who received the combination. The overall response rate by National Prostatic Cancer Project Criteria was 53% for doxorubicin and 59% for doxorubicin plus cisplatin. Myelotoxicity and gastrointestinal toxicity were severe, particularly in the combination arm, and required discontinuation of treatment in some patients who responded to treatment. Moderate renal dysfunction (creatinine value 2.0-3.0 mg/dl) occurred only in the combination arm at an incidence of 23%. Time to progression and survival were similar for the two treatment groups. In this small group of 37 patients, the combination of cisplatin and doxorubicin showed no improvement over doxorubicin alone in response, response duration, or survival, and was difficult to administer in this patient population.
Adenocarcinoma↗
Gynecomastia in testicular cancer patients. Prognostic and therapeutic implications.
Eighty-one patients with advanced testicular cancer were evaluated for gynecomastia or severe breast tenderness at diagnosis and after platinum-based chemotherapy. The prognostic significance of gynecomastia in these two settings was explored. At presentation, 10% (8 patients) had gynecomastia or breast tenderness and elevated HCG levels. The likelihood of gynecomastia was greater with increasing HCG level (P = 0.002). However, gynecomastia at presentation was a more powerful independent discriminant of poor survival than the initial HCG level by multivariate analysis (P = 0.004). Fifteen percent (12 patients) developed transient gynecomastia after chemotherapy not attributable to other known causes. HCG levels were normal. Endocrine evaluation typically revealed elevated FSH, LH, and estradiol/testosterone ratios. This may have reflected damage to testicular germinal epithelium. All 12 patients are alive without disease in contrast to the 8 patients who had gynecomastia at diagnosis. Therapy decisions should therefore be based on the time of onset of gynecomastia and in the context of appropriate clinical markers and evaluation.
Adolescent↗
A macrophage factor inhibits adipocyte gene expression: an in vitro model of cachexia.
Certain infections and malignancies in mammals cause the development of a condition known as cachexia in which the animal continues to lose weight, often while consuming an adequate diet. When macrophages are stimulated with an endotoxin, they produce a factor or factors, termed cachectin, that inhibits the activity of fat-producing (lipogenic) enzymes in cultured adipocytes. This effect may reflect one of the physiological bases for cachexia. In the present study, clones of complementary DNA from genes whose expression is increased during the differentiation of adipocytes were used to study the molecular basis of cachectin's actions. In the presence of cachectin, the expression of the corresponding genes was reversibly and specifically inhibited. Furthermore, when mature adipocytes were exposed to cachectin, the messenger RNA's of those genes diminished and rapidly approached the levels present before differentiation.
Actins↗
The fate of the bladder in patients with metastatic bladder cancer treated with cisplatin, methotrexate and vinblastine: a Northern California Oncology Group study.
We report the efficacy and toxicity of combined cisplatin, methotrexate and vinblastine for the treatment of metastatic transitional cell carcinoma of the bladder in 50 evaluable patients. Of these 50 patients 17 had not undergone cystectomy and had residual invasive bladder cancer. Of these 17 patients 11 had complete response of the bladder lesions following cisplatin, methotrexate and vinblastine for metastatic disease, including 6 of 12 treated by cisplatin, methotrexate and vinblastine alone, and 5 of 5 treated with cisplatin, methotrexate and vinblastine plus palliative or preoperative pelvic irradiation. Complete response was confirmed in 10 of the 11 patients by endoscopy and biopsy, and in 1 by cystectomy. One patient whose liver metastasis responded to cisplatin, methotrexate and vinblastine had conversion to complete response by cystectomy for persistent bladder cancer. Of these 17 patients 7 are alive, including 5 without disease, 4 to 41 months after treatment. The bladder appears to be responsive to this combination chemotherapy for invasive transitional cell carcinoma. This experience underscores the need for regular pathological re-staging of the bladder cancer in patients receiving chemotherapy.
Antineoplastic Combined Chemotherapy Protocols↗
Doxorubicin: alteration of dose scheduling as a means of reducing cardiotoxicity.
The long-term therapeutic potential of doxorubicin is often limited by the predictable development of a dose-related cardiomyopathy. Empiric limitations of cumulative doses to 450-550 mg/m2 minimize the incidence of this potentially fatal toxicity. This review presents recent studies performed to examine the potential for altered dose schedule to reduce or delay this toxicity and maintain therapeutic efficacy. Altering doxorubicin's dosing schedule from the standard three-weekly regimen to a continuous infusion or weekly schedule has been shown to delay cardiotoxicity. Data presented suggest that doxorubicin administered on a weekly schedule significantly reduces cardiotoxicity as compared with a three-weekly schedule and allows approximately 160 mg/m2 more of the drug to be administered to reach the same level of cardiotoxicity as measured by endomyocardial biopsy. This corresponds clinically to two additional months of therapy. Cumulated response data suggest that continuous infusion or weekly schedules of doxorubicin are equally efficacious as the standard three-weekly schedule.
Doxorubicin↗