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Biomedical subjects

N A Dawson

Publications and source records attributed to N A Dawson.

12 recordsLinked to original sources
PubMed1995

Antitumor activity of suramin in hormone-refractory prostate cancer controlling for hydrocortisone treatment and flutamide withdrawal as potentially confounding variables.

BACKGROUND: A prospective Phase II clinical trial was conducted to assess the clinical activity of a pharmacokinetically guided suramin regimen in patients who had documented progression of metastatic prostate cancer after hydrocortisone plus antecedent or simultaneous withdrawal of flutamide. METHODS: Fifty-four patients whose disease had progressed after castration and flutamide administration were enrolled on this trial. The study was divided into two parts. Initially, 52 patients received hydrocortisone (30 mg/day) and for those patients receiving flutamide, at study entry (34 patients) flutamide was simultaneously discontinued. Forty-three patients whose disease progressed on hydrocortisone received suramin for 6-8 weeks. Six patients who progressed on hydrocortisone became ineligible for suramin due to clinical deterioration, four patients are still responding to hydrocortisone at more than 1 year, and one patient elected to postpone initiation of suramin. Suramin was given as intermittent infusions at fixed doses on days 1-5 and thereafter dosing was guided by adaptive control with feedback to maintain plasma suramin concentrations between 300-175 micrograms/ml. Antitumor activity was assessed by prostate specific antigen (PSA) decline and soft-tissue disease response. RESULTS: Ten patients (19%; 95% CI, 9.6%-32.5%) responded to hydrocortisone therapy with either a 50% or greater PSA decline for at least 4 weeks (9 patients) and/or a partial response of measurable soft-tissue disease (2 patients). Five of these patients (10%) demonstrated a 80% or greater PSA decline. All responders to hydrocortisone had simultaneous flutamide withdrawal, and had been receiving flutamide as part of initial combined androgen blockade. Seven of 37 evaluable patients (19%; 95% CI, 8.0%-35.2%) responded to suramin with a 50% or greater decline in PSA for 4 weeks or longer. One patient (3%) had a 80% or greater decline in PSA. There were no soft-tissue disease responses to suramin. The median time to progression was 1.9 months for hydrocortisone therapy and 2.6 months for suramin therapy. The median survival for all patients was 14.6 months. CONCLUSION: Suramin has antitumor activity in metastatic prostate carcinoma independent of the therapeutic effect of hydrocortisone administration or flutamide withdrawal. The role of prior flutamide withdrawal and hydrocortisone replacement should be taken into account in future studies of suramin.

Aged↗
PubMed1995

Extramedullary myeloid cell tumors in acute nonlymphocytic leukemia: a clinical review.

PURPOSE: To discuss the predisposing risk factor for all forms of extramedullary leukemia (EML) and to review the clinical features, prognostic significance, and treatment strategies for primary EML and leukemia cutis (LC)/granulocytic sarcomas (GS) in the setting of acute nonlymphocytic leukemia (ANLL). METHODS: A review of all reports published since 1965 related to all forms of extramedullary leukemia (LC, GS, gingival hypertrophy, and meningeal leukemia [ML]). RESULTS: Several factors, including chromosomal abnormalities [t(8;21), inv(16)], cell-surface markers (CD56, CD2, CD4, CD7), French-American-British (FAB) subtype (M2, M4, M5), blast differentiation and maturation, patient nutritional status, age, cellular immune dysfunction, high presenting leukocyte count, and decreased blast Auer rods, have been associated with a higher incidence of EML. Of 154 published cases of primary EML identified, 71 (46%) were initially misdiagnosed. The addition of immunohistochemical stains can assist in preventing such misdiagnoses and should be included in all atypical lymphoma/carcinoma cases. Only one of the patients (3%) with primary EML did not progress to ANLL in the absence of chemotherapy. In contrast, 66% of patients who received chemotherapy for the primary EML never developed ANLL. The prognostic significance of EML at presentation and medullary relapse of ANLL is uncertain. Isolated extramedullary recurrence of ANLL always heralds bone marrow relapse and should be treated with reinduction chemotherapy. Close clinical follow-up observation is necessary to insure resolution of EML. Radiation therapy is an effective local treatment for resistant or symptomatic EML. CONCLUSION: Many advances in diagnoses and treatment of EML have been made. Future investigations are needed to define the clinical significance of EML in patients with ANLL treated with modern chemotherapy or bone marrow transplantation.

Age Factors↗
PubMed1993

Treatment of progressive metastatic prostate cancer.

The optimal therapy for metastatic prostate cancer that has failed initial hormonal therapy poses a significant dilemma for the attending physician. No salvage therapy has proven to be clearly superior. Currently accepted treatment options range from supportive care alone to highly investigational regimens. Recent encouraging results have been reported with investigational agents such as suramin and R. 75251 (Liarozole), and with novel combinations such as estramustine (Emcyt) plus vinblastine. However, there is still no proof that salvage therapy prolongs survival. In a patient population that is older and frequently debilitated, with an expected median survival of 6 months, determinants of therapy should include drug toxicity profiles, frequency of treatment and follow-up studies, and necessity for hospitalization. For patients with good performance status and organ function, participation in clinical trials should be advocated. Quality-of-life issues should be integrated into all clinical trials involving hormone-refractory metastatic prostate cancer.

Androgen Antagonists↗
PubMed1992

A pilot trial of chemohormonal therapy for metastatic prostate carcinoma.

Fifteen patients with previously untreated metastatic prostate cancer were treated on a pilot trial with a combination of maximal androgen blockade plus intermittent cytotoxic therapy after androgen priming to stimulate cell division. Androgen blockage was carried out using a gonadotropin-releasing hormone analog (leuprolide) plus a nonsteroidal antiandrogen (flutamide). Carboplatin (CBDCA) (800 mg/m2) was given intravenously every 28 days, preceded for 3 days and followed for 3 days by androgen treatment with fluoxymesterone (5 mg orally twice a day), during which time flutamide was discontinued. Three patients (20%) achieved a complete response (CR), and eight patients (53.3%) achieved a partial response (PR). Four patients (26.7%) had stable disease (SD). The median progression-free survival (PFS) time was 31 months. Nine of 15 patients (60%) remain alive with a median follow-up time of 42+ months (range, 22 to 54 months). Grade 4 thrombocytopenia and Grades 3 or 4 leukopenia were experienced in 87% and 80% of patients, respectively, requiring dose reductions of CBDCA in 85% of the cycles. Six of 15 patients experienced a flare in bone pain with androgen priming. There were no associated spinal cord compressions; however, exclusion of impending spinal cord compression was required before entrance on study.

Adenocarcinoma↗
PubMed1992

Suramin-induced skin reactions.

BACKGROUND AND DESIGN: Suramin sodium, a polysulfonated naphthylurea, has been used for more than 70 years as a chemotherapeutic agent for a variety of diseases. In a phase II trial of suramin, 20 patients with metastatic prostate carcinoma refractory to hormonal manipulation were evaluated retrospectively for evidence of skin toxicity. RESULTS: Three types of skin reaction were noted: generalized, erythematous, maculopapular eruption (10 patients); keratoacanthoma (two patients); and disseminated superficial actinic porokeratosis (one patient). A total of 15 episodes of some form of skin reaction occurred in 13 patients. The maculopapular eruptions resolved in 3 to 5 days despite continued treatment with suramin. CONCLUSIONS: Cutaneous toxicity was a frequent and, often, self-limited side effect of suramin therapy, occurring in 13 (65%) patients. Keratoacanthoma and disseminated superficial actinic porokeratosis have not previously been reported to occur with suramin therapy. The immunosuppressive effect of suramin may induce the keratoacanthoma and disseminated superficial actinic porokeratosis lesions.

Carcinoma↗
PubMed1991

Trimetrexate in untreated and previously treated patients with metastatic breast cancer: a Cancer and Leukemia Group B study.

Twenty-two patients with previously untreated metastatic breast cancer and nineteen patients with refractory metastatic breast cancer were treated with trimetrexate (TMTX). Patients received TMTX 8 mg/m2/day if previously treated or 12 mg/m2/day if previously untreated, both given by intravenous bolus days 1-5, every 21 days. None of the patients previously treated for metastatic disease responded to TMTX. There was one partial responder among the 22 patients with previously untreated metastatic disease. The primary toxicity was hematologic and occurred more frequently in patients with a pleural effusion, low serum protein or albumin, or poor performance status. There were three toxic deaths. The study for previously untreated patients required cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) after 4 cycles of TMTX. This study design for previously untreated patients allows the Cancer and Leukemia Group B (CALGB) to prospectively evaluate the activity of new agents in "chemotherapy-sensitive" metastatic breast cancer.

Antineoplastic Agents↗
PubMed1988

Salvage therapy in metastatic adult Wilms' tumor.

Adult Wilms' tumor is a rare and aggressive malignancy. Despite multimodality therapy for all stages of disease, the majority of patients develop fatal metastases. Little information is available on effective salvage therapy. The current report describes a 38-year-old man who had Stage I disease. Pulmonary metastases developed after radical nephrectomy and tumor bed irradiation while receiving adjuvant chemotherapy. He achieved a complete remission lasting 8 months with a combination chemotherapy regimen of cyclophosphamide, vinblastine, dactinomycin, and cisplatin. After isolated pulmonary relapse, he received whole-lung irradiation and remained disease-free 4.5 years after diagnosis. The previously reported results of therapy in metastatic or unresectable adult Wilms' tumor are reviewed, and the current case of effective salvage therapy is documented.

Adult↗
PubMed1988

Clinical predictors of response in metastatic germ cell tumors.

Twenty-two patients with bulky, metastatic germ cell tumors were treated with cyclophosphamide, vinblastine, dactinomycin, bleomycin, and cisplatin (VAB) alternating with VP-16 and vincristine (VV). The overall complete response rate after chemotherapy with or without surgical excision of residual tissue was 63% (14 of 22 patients) with a median survival of 46 months. Five patients are dead of disease progression and three are alive beyond 3 years with only residual radiographic abnormalities. A retrospective analysis of prognostic variables (numbers of sites of disease, tumor marker levels) using two previously published prognosis formulas demonstrated a good correlation between prognostic variables (numbers of sites of disease, tumor marker levels) and the clinical assessment of prognosis based on tumor bulk and tumor marker level. Nevertheless, individual patients with other, unknown prognostic features may be incorrectly evaluated using either established formulas or clinical assessment of tumor bulk.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Extragonadal germ cell tumors. Clinicopathologic findings and treatment experience in 12 patients.

In patients with primary germ cell tumors, treatment with combination chemotherapy followed by surgical debulking of residual tissue usually produces favorable results. The best treatment for patients with extragonadal germ cell tumors (EGCT) remains a problem. In our series of 12 patients, important clinical features were related to the site of bulky tumor, and all patients exhibited sharply elevated levels of lactate dehydrogenase (LDH), beta subunit human chorionic gonadotropin (beta-HCG), and/or alpha-fetoprotein (AFP). Each patient was treated with systemic chemotherapy, and ten were treated with the same combination chemotherapy--cyclophosphamide, actinomycin, vinblastine, bleomycin, and cisplatin (VAB) alternating with VP-16 and vincristine (VV). Of these ten patients, five died of progressive disease, three of whom had brain metastases. The other five are alive and clinically free of disease. The addition of VP-16 and vincristine did not improve responses. Advanced disease at presentation contributes to the poorer prognosis for these patients. Earlier diagnosis and surgical debulking may improve the long-term survival of patients with this disease.

Adult↗
PubMed1988

Angioendotheliomatosis.

"Angioendotheliomatosis" is a diagnostic term used in histopathology to describe the proliferation of dilated vessels filled with mononuclear cells that have varying degrees of atypia. Either benign or malignant angioendotheliomatosis may exhibit this histologic pattern, and depending on the clinical course, cases are classified as either reactive angioendotheliomatosis or neoplastic angioendotheliomatosis. A case of neoplastic angioendotheliomatosis is presented and the literature reviewed with special attention to the pathogenesis of this condition.

Brain Neoplasms↗
PubMed1985

Acquired dysfibrinogenemia. Paraneoplastic syndrome in renal cell carcinoma.

Acquired dysfibrinogenemia has not been previously reported as a paraneoplastic marker for malignancy. This report describes the clinical course of a patient who at the time of diagnosis of nonmetastatic renal cell carcinoma had dysfibrinogenemia characterized by prolongation of the thrombin and Reptilase times and increased sialic acid content of the purified fibrinogen. The thrombin and Reptilase times returned toward normal values after nephrectomy but became abnormal with the development of nonhepatic metastases. It is concluded that acquired dysfibrinogenemia can be part of a paraneoplastic syndrome and is a sensitive plasma marker for tumor progression.

Carcinoma, Renal Cell↗