Phase II trial of intermediate dose methotrexate in combination with vinblastine, doxorubicin, and cisplatin in patients with unresectable or metastatic transitional cell carcinoma.

Background: This study was undertaken to determine whether the use of intermediate dose methotrexate in combination with vinblastine, doxorubicin, and cisplatin as first-line therapy increases the proportion of major responders and overall survival in patients with unresectable or metastatic transitional cell carcinoma (TCC) of the urothelial tract.

Methods: Twenty-nine patients with histologically confirmed TCC received methotrexate at a dose of 1000 mg/m2 on Day 1 followed by leucovorin calcium rescue on Day 2 and vinblastine (3 mg/m2), doxorubicin (30 mg/m2), and cisplatin (70 mg/m2) (VAC) on Day 2. Therapy was recycled at 28-day intervals.

Aminopeptidase A expression and enzymatic activity in primary human renal cancers.

The gp160 human kidney differentiation antigen is identical to human aminopeptidase A (APA), a zinc-dependent cell-surface metallopeptidase which hydrolyzes peptides with N-terminal acidic residues. GP160/APA is constitutively expressed by proximal tubule cells, the normal cellular counterpart of most renal cancers (RCs). Immunohistochemical analysis of gp160/APA protein expression in 62 primary renal tumor specimens using monoclonal antibody S4 revealed heterogeneous or homogeneous expression of gp160/APA in 46/51 (90%) of clear cell carcinomas in contrast with 1/8 (13%) papillary renal tumors and 0/3 oncocytomas (p<0.

Differentiated thyroid cancer: determinants of disease progression in patients <21 years of age at diagnosis: a report from the Surgical Discipline Committee of the Children's Cancer Group.

Objective: This study was done to define the extent of disease and evaluate the effect of staging and treatment variables on progression-free survival in patients with differentiated thyroid carcinoma who were less than 21 years of age at diagnosis.

Summary Background Data: Differentiated thyroid cancer in young patients is associated with early regional lymph node involvement and distant parenchymal metastases. Despite this, the overall long-term survival rate is greater than 90%, which suggests that biologic rather than treatment factors have a greater effect on outcome.

Metastatic germ cell tumors: modeling for response to chemotherapy.

Purpose: This study sought to determine factors that predict response to chemotherapy for patients with advanced germ cell tumors (GCTs), to evaluate different methods by which serum tumor markers can be used to predict response independent of assay method, and to develop criteria to guide allocation to clinical trials.

Methods: Pretreatment data from 796 patients treated with platinum-based chemotherapy on Memorial Hospital protocols from 1975 to 1990 were analyzed. Multivariate analyses were performed on a developmental data set (n = 597) to assess for independently significant predictors of response.

Ifosfamide- and cisplatin-containing chemotherapy as first-line salvage therapy in germ cell tumors: response and survival.

Purpose: To evaluate the efficacy and toxicity of ifosfamide- and cisplatin-containing chemotherapy as first-line salvage treatment for patients with germ cell tumors (GCT).

Patients And Methods: Fifty-six patients with advanced GCT resistant to one prior cisplatin-containing regimen were treated with a salvage chemotherapy regimen of ifosfamide, cisplatin, and either vinblastine or etoposide (VeIP/VIP).

Results: Twenty of 56 (36%) assessable patients achieved a complete response (CR).

Long-term follow-up of patients with good-risk germ cell tumors treated with etoposide and cisplatin.

Purpose: To assess the durability of response and overall survival for patients with good-risk metastatic germ cell tumors (GCT) treated with four cycles of etoposide and cisplatin (EP).

Patients And Methods: Two hundred fourteen patients treated with EP on two consecutive randomized trials for good-risk metastatic GCT were the subject of this retrospective study. The response to therapy, relapse and survival status, and results of salvage therapy are reported.

High-dose carboplatin, etoposide, and cyclophosphamide with autologous bone marrow transplantation in first-line therapy for patients with poor-risk germ cell tumors.

Purpose: A treatment program that included high-dose carboplatin, etoposide, and cyclophosphamide (CEC) followed by autologous bone marrow transplantation (AuBMT) was investigated as first-line therapy in patients with poor-risk germ cell tumors (GCTs).

Patients And Methods: Previously untreated GCT patients with poor-risk features were treated with etoposide, ifosfamide, and cisplatin (VIP) with or without high-dose CEC plus AuBMT. Patients qualified for a change to high-dose CEC if a prolonged clearance of elevated serum tumor markers was observed after two cycles of the cisplatin-containing regimen.

A phase II study of 13-cis-retinoic acid in patients with advanced renal cell carcinoma.

The aim of this study was to determine the antitumor activity of 13-cis-retinoic acid as a single agent in patients with advanced renal cell carcinoma. Eligible patients had advanced renal cell carcinoma with bi-dimensionally measurable disease, a Karnofsky performance status of at least 70, life expectancy of greater than three months, no evidence of brain metastases, and treatment with no more than one chemotherapy regimen. Patients were treated with one mg/kg/day of 13-cis-retinoic acid orally.

Chemotherapy without irradiation--a novel approach for newly diagnosed CNS germ cell tumors: results of an international cooperative trial. The First International Central Nervous System Germ Cell Tumor Study.

Purpose: Radiation therapy for CNS germ cell tumors (GCT) is commonly associated with neurologic sequelae. We designed a therapeutic trial to determine whether irradiation could be avoided.

Patients And Methods: Patients received four cycles of carboplatin, etoposide, and bleomycin.

Acid phosphatase: defining a role in androgen-independent prostate cancer.

Objectives: In multivariable analysis, post-therapy change in prostate-specific antigen (PSA) was shown to be the most significant factor predictive of survival in patients with androgen-independent prostate cancer. To refine the model, we studied the patterns of change in acid phosphatase, alkaline phosphatase, and lactate dehydrogenase after treatment.

Methods: One hundred seven patients with androgen-independent prostate cancer treated on seven different protocols in Memorial Sloan-Kettering Cancer Center were evaluated.

High-dose carboplatin, etoposide, and cyclophosphamide for patients with refractory germ cell tumors: treatment results and prognostic factors for survival and toxicity.

Purpose: The efficacy and toxicity of high-dose carboplatin, etoposide, and cyclophosphamide with autologous bone marrow transplantation (AuBMT) was investigated in a prospective trial for patients with cisplatin-refractory germ cell tumor (GCT). Prognostic factors for survival and treatment-related toxicity were identified.

Patients And Methods: Fifty-eight patients with refractory GCT were treated with high-dose carboplatin, etoposide, and cyclophosphamide plus AuBMT.

Management of residual mass in advanced seminoma: results and recommendations from the Memorial Sloan-Kettering Cancer Center.

Purpose: Guidelines for management of postchemotherapy residual mass in patients with advanced seminoma remain controversial. We sought to characterize independent prognostic factor(s) for persistence of tumor to identify patients with a high risk of residual carcinoma.

Patients And Methods: One hundred four patients with advanced seminoma were assessed.

Etoposide and cisplatin adjuvant therapy for patients with pathologic stage II germ cell tumors.

Purpose: Two options cure nearly all patients with pathologic stage II nonseminomatous germ cell tumors (NSGCTs): two cycles of adjuvant chemotherapy with cisplatin, vinblastine, and bleomycin (PVB) or cisplatin, vinblastine, bleomycin, cyclophosphamide, and dactinomycin (VAB-6); or close observation with full treatment at relapse. Two cycles of etoposide plus cisplatin (EP) were given to selected patients with pathologic stage II NSGCT and high-volume nodal metastases.

Patients And Methods: All patients had pathologic stage II NSGCT with one or more of the following features found at retroperitoneal lymph node dissection (RPLND), suggesting a greater than 50% likelihood of relapse after observation alone: (1) any lymph node involved by tumor greater than 2 cm (stage N2b); (2) > or = six nodes involved with tumor (stage N2b); and (3) extranodal extension (stage N3).

Quality of life of women with ovarian cancer.

The primary objectives of this study were to determine the nature and extent of physical problems and psychological distress experienced by women with ovarian cancer and to identify medical and sociodemographic factors that were predictive of distress. Quality of life was assessed at 3-month intervals, for a maximum of 12 months in 151 ovarian cancer patients, most with advanced-stage disease (86%). Patients' pain, other physical symptoms, level of physical functioning, psychological state, and social functioning were evaluated using the following measures: a detailed pain questionnaire, Memorial Pain Assessment Card, Memorial Symptom Assessment Scale, Mental Health Inventory (MHI), Functional Living Index--Cancer (FLIC), and the Karnofsky Performance Status.

Phase III randomized trial of interleukin-2 with or without lymphokine-activated killer cells in the treatment of patients with advanced renal cell carcinoma.

Background: Treatment with interleukin-2 (IL-2) and lymphokine-activated killer cells (LAK) resulted in responses in some patients with advanced renal cell carcinoma (RCC). However, the relative therapeutic benefit of the addition of LAK to IL-2 was unknown.

Methods: A randomized Phase III trial was conducted in patients with RCC comparing continuous intravenous infusion (CI) IL-2 alone with CI IL-2 plus LAK.

Suramin and hydrocortisone: determining drug efficacy in androgen-independent prostate cancer.

Purpose: The combination of suramin and hydrocortisone has shown clinical benefit in patients with androgen-independent prostate cancer. Widespread use was limited by the complex dose schedules and the need for pharmacologic monitoring. This study reports three sequential pharmacokinetically derived treatment regimens that simplified the administration of suramin and hydrocortisone with reduced toxicity.

Interferon alfa-2a and 13-cis-retinoic acid in renal cell carcinoma: antitumor activity in a phase II trial and interactions in vitro.

Purpose: A phase II trial of interferon alfa-2a (IFN) and 13-cis-retinoic acid (CRA) was conducted in patients with renal cell carcinoma (RCC). In vitro studies were performed to investigate potential mechanisms of interaction.

Patients And Methods: Forty-four patients were treated.

Cytoreductive surgery in ovarian carcinoma patients with a documented previously complete surgical response.

Recurrent ovarian cancer after negative findings at second-look laparotomy is common. A retrospective review of 57 patients who developed recurrent tumor after a negative second-look laparotomy was undertaken to evaluate treatment efficacy and prognostic factors. All patients received primary platinum-based chemotherapy.

Tamoxifen use in breast cancer patients who subsequently develop corpus cancer is not associated with a higher incidence of adverse histologic features.

Several reports have noted an association between the use of tamoxifen in breast cancer patients and the subsequent development of endometrial carcinoma. Magriples et al. (J.

Pain in ovarian cancer patients. Prevalence, characteristics, and associated symptoms.

Background: The prevalence, characteristics, and impact of pain and other symptoms have not been studied systematically in women with ovarian cancer. Anecdotally, pain has been associated with the onset of the disease and is a common problem among those with advanced cancer; symptoms other than pain appear to be highly prevalent. Given the profound influence of pain and other symptoms on quality of life, the evaluation of these phenomena could provide data relevant to the clinical management of these patients and advance quality of life research in the area of symptom assessment.

Serum tumor marker decline is an early predictor of treatment outcome in germ cell tumor patients treated with cisplatin and ifosfamide salvage chemotherapy.

Background: Serum tumor marker regression (alpha-fetoprotein [AFP] and human chorionic gonadotrophin [hCG]) was studied in patients treated with ifosfamide-based chemotherapy for cisplatin-resistant germ cell tumors (GCT) to investigate the role of marker regression as a predictor of treatment outcome.

Methods: Fifty-four patients treated with cisplatin and ifosfamide-containing therapy were the subject of this retrospective analysis. The serum tumor marker half-life (T1/2) for the first two cycles of therapy was calculated for each patient using all marker values Day 7 through the end of the second treatment cycle.

The effect of age at diagnosis on outcome in rhabdomyosarcoma.

Background: Survival for rhabdomyosarcoma appears to be more favorable in children and adolescents compared with adults. To determine the significance of age at diagnosis as a prognostic indicator in rhabdomyosarcoma, we performed a retrospective analysis of a combined pediatric and adult rhabdomyosarcoma data base.

Methods: Pertinent prognostic variables, including age, TNM stage, histopathologic subtype, anatomic site, resectability, radiation to the primary site, and dose intensity of chemotherapy, were compared in a Cox proportional hazards model with mortality as the outcome variable.

Advanced seminoma: treatment results, survival, and prognostic factors in 142 patients.

Purpose: To investigate the efficacy of chemotherapy and to assess the relationship between selected pretreatment characteristics and survival in patients with advanced seminoma.

Patients And Methods: One hundred forty-two patients with advanced seminoma treated with platinum-based chemotherapy were the subject of this study. Treatment regimens included cisplatin, vinblastine, bleomycin, cyclophosphamide, and dactinomycin (VAB-6) (45 patients), a six-cycle regimen of VAB-6 alternating with etoposide and cisplatin (two patients), cisplatin and etoposide (60 patients), and etoposide and carboplatin (35 patients).

Phase II trial of high-dose carboplatin and etoposide with autologous bone marrow transplantation in first-line therapy for patients with poor-risk germ cell tumors.

Background: Between 20% and 30% of patients with advanced germ cell tumors (GCTs) fail to have durable complete response to conventional cisplatin-based induction chemotherapy. However, third-line therapy with high-dose carboplatin and etoposide plus autologous bone marrow transplantation (AuBMT) has induced durable complete response in 10%-20% of patients with cisplatin-resistant GCT.

Purpose: We conducted a phase II trial of first-line therapy that included high-dose carboplatin and etoposide plus AuBMT in untreated men with advanced GCTs and unfavorable prognosis (i.