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Biomedical subjects

D J Adelstein

Publications and source records attributed to D J Adelstein.

At least 73 records · Page 4Linked to original sources
PubMed1988

Thromboembolic events in patients with malignant superior vena cava syndrome and the role of anticoagulation.

In patients with superior vena caval obstruction resulting from malignancy, the importance of vena caval thrombosis and the role of anticoagulation are incompletely understood. The authors discuss this aspect of the management of 25 patients with malignant superior vena cava syndrome. Ten patients were retrospectively reviewed after having been clinically diagnosed without venography, and treated without anticoagulation. Five thromboembolic complications occurred, two of which proved fatal. Fifteen patients were prospectively evaluated by angiography and then treated with anticoagulants. Angiographic evidence of intraluminal subclavian vein or superior vena caval thrombosis was found in five of these patients, and no thromboembolic complications occurred. Of the 20 patients ultimately anticoagulated, two fatal intracranial hemorrhages developed. The authors suggest the need for randomized prospective trials if the role of venography and anticoagulation in this syndrome is to be determined.

Anticoagulants↗
PubMed1988

Pneumonia carcinomatosa from small cell undifferentiated carcinoma of the lung presenting as "reverse radiation pneumonitis".

We describe a patient with recurrent small cell undifferentiated lung carcinoma after chemotherapy and mediastinal radiation therapy who presented with peripheral pulmonary infiltrates on chest radiograph. At autopsy the patient was found to have carcinomatous pneumonia confined to the radiographically abnormal lung. The descriptive term "reverse radiation pneumonitis" is applied in view of the striking nonsegmental distribution of these pulmonary infiltrates, which occurred only outside the irradiated field. In this patient, radiation therapy successfully controlled disease in the treated lung parenchyma, thus accounting for this unusual radiologic and histologic picture. Pneumonia carcinomatosa, occurring after lung irradiation, can therefore be added to the differential diagnosis of radiographic peripheral pulmonary infiltrates.

Aged↗
PubMed1988

Multiple myeloma presenting with spinal cord compression.

The clinical features, treatment, and course of 6 patients with multiple myeloma, who presented initially with spinal cord compression, are reviewed. These 6 represent 12% of all patients with myeloma seen at our institution since 1979. Eighty-three similar patients were identified from the medical literature. There are no patient characteristics predictive for this presentation. A higher than expected proportion of patents have clinically localized disease, but progression to myelomatosis is common. As these patients present without a known diagnosis of malignancy, a prompt, invasive diagnostic procedure and the immediate institution of definitive local therapy is mandatory. Despite such an aggressive approach, the prospect for significant return of neurologic function is poor. Survival does not appear to be different from that of other patients with myeloma. Unlike other malignancies, a presentation with cord compression is not inconsistent with long-term survival, although significant morbidity secondary to the resultant functional disability can be expected.

Adult↗
PubMed1988

Treatment of advanced-stage colorectal adenocarcinoma with fluorouracil and high-dose leucovorin calcium: a pilot study.

Thirty-one evaluable patients with measurable advanced colorectal carcinoma were entered into a pilot study that used weekly fluorouracil (5-FU) at the dose of 600 mg/m2 by bolus infusion administered midway during a two-hour leucovorin calcium infusion of 500 mg/m2. This regimen was repeated weekly for six doses. Twenty-seven of these patients (87%) were considered to be refractory to prior 5-FU therapy and four (13%) were previously untreated. All 31 patients successfully completed at least one 6-week cycle of this regimen with acceptable toxicity. The combined complete (CR) and partial response (PR) rate was 45% with another 25% of patients remaining stable. The 95% confidence levels for the responding patients are 27.6% and 62.7%, respectively. The remaining 30% of the patients had all received prior 5-FU therapy and progressed. All of the responding patients and 80% of the patients with stable disease received two or more cycles of this regimen after a 3- to 4-week interval off therapy. The median time to disease progression was 16.1 months for responding patients and 6.7 months for those patients with stable disease. The median survival for the responders was 20.6 months and for those with stable disease 9.8 months. The median survival for the nonresponding patients was 3.9 months. Toxicity included diarrhea in 70% of patients, skin rash (erythema) in 10%, stomatitis in 15%, nausea and vomiting in 25%, and myelosuppression in 10%. This study confirms and extends previous observations that demonstrate the improved efficacy of 5-FU when used with high-dose leucovorin in advanced colorectal carcinoma.

Adenocarcinoma↗
PubMed1988

Simultaneous radiotherapy and chemotherapy with 5-fluorouracil and cisplatin for locally confined squamous cell head and neck cancer.

Fifty-four patients with previously untreated or minimally treated locally confined (MO) squamous cell carcinoma of the head and neck were treated with chemoradiotherapy employing multiple courses of simultaneous radiation, cisplatin, and a 4-day 5-fluorouracil infusion. Twenty-eight patients subsequently underwent definitive surgery, and 26 were treated without surgical resection. Of the 54 patients, 51 were ultimately rendered disease free by this combined modality protocol. The projected relapse-free survival rate for the entire cohort is 71%, with a median relapse-free survival time greater than 17 months. Thirteen patients who had tumors that were technically operable did not undergo surgery after achieving a complete response to induction chemoradiotherapy. Only 1 of these patients experienced subsequent local failure. Although the treatment-associated mucositis and local failure. Although the treatment-associated mucositis and myelosuppression were significant, this chemoradiotherapeutic protocol offers a significant chance of relapse-free survival for all patients with locally confined disease and merits comparison with more standard treatment approaches.

Adult↗
PubMed1987

Intramedullary spinal cord metastasis. Diagnostic and therapeutic considerations.

The diagnosis of intramedullary spinal cord metastasis (ISM) is difficult, and treatment is usually ineffective. We review our own experience with ISM as well as the pertinent medical literature, and suggest a practical diagnostic and therapeutic approach. The problem of the diagnosis of ISM is essentially that of the differential diagnosis of a noncompressive myelopathy in a patient with systemic cancer. Most such patients prove to have ISM, meningeal carcinomatosis, radiation myelopathy, or paraneoplastic necrotizing myelopathy. Neurologic features of value in this differential diagnosis are pain, the tempo and mode of progression of symptoms, and tumor cells in the spinal fluid. Oncologic features of value are the location of the primary tumor, the past exposure to therapeutic radiation, cerebral metastases, and the extent of systemic metastatic disease. The myelogram in ISM is either normal or nonspecifically abnormal; therefore, the diagnosis must be made on clinical grounds. Although no single finding is diagnostic of ISM, a careful clinical analysis will lead to the correct diagnosis in most cases. Radiation therapy is effective treatment for ISM, but only if it is administered early, before paraplegia supervenes. Thus, the diagnosis should be made and treatment begun as soon as possible. Intramedullary spinal cord metastasis is often multifocal rather than solitary; therefore, whole-cord rather than local spinal radiation should be given, if possible. If local radiotherapy is chosen, the construction of the portal can be based on the myelogram or, in the event of a normal study, on the clinical localization of the tumor.

Diagnosis, Differential↗
PubMed1987

The role of surgery in the management of selected patients with small-cell carcinoma of the lung.

This study was designed to evaluate the efficacy of surgical resection of the primary tumor and lymph nodes in patients with localized small-cell carcinoma who had responded to induction chemotherapy. The study was performed in 37 patients who received two cycles of chemotherapy consisting of cyclophosphamide, doxorubicin, and etoposide. Those patients who achieved a complete or partial (greater than 50%) response were evaluated for thoracotomy and the primary tumor and regional lymph nodes excised when feasible. Postoperatively, the patients received prophylactic cranial irradiation and were maintained on the same chemotherapy for an average of 11 months. Twelve patients were resected and found to have residual small-cell carcinoma in the operative specimen (ten) or no residual disease (two). Seven of these patients (58%) are alive without evidence of disease (median follow-up, 24 months). Seven other patients who were resected proved to have either residual foci or small-cell carcinoma mixed with adenocarcinoma or large-cell carcinoma (four) or only focal areas of adenocarcinoma, large-cell carcinoma, or squamous-cell carcinoma with no evidence of residual small-cell carcinoma. Five of these patients (71%) are alive without evidence of disease (median follow-up, 36 months). Two of the 16 patients who were not resected but treated with chemotherapy and radiation are alive at 15 and 31 months without evidence of disease, the other 14 are dead of disease.

Adult↗
PubMed1987

Cerebellar toxicity with high-dose cytosine arabinoside.

CNS dysfunction, especially impaired cerebellar function, is the dose-limiting toxicity associated with high-dose cytosine arabinoside, which precludes doses of greater than 48 g/m2. Four hundred eighteen patients between the ages of 2 and 74 years with leukemia or lymphoma received 36 to 48 g/m2 cytosine arabinoside either alone or with anthracycline antibiotics, 4'-(9-acridinylamino) methane sulfon-m-anisidine (m-AMSA), or total body irradiation. In only 35 of 418 patients (8%) did severe cerebellar toxicity develop; it was irreversible or fatal in four (1%) patients. The age of the patient was a critical factor in the incidence of severe cerebellar toxicity. Patients greater than 50 years old had a statistically significant greater incidence of cerebellar toxicity compared with younger patients (26/137, 19%, v 9/281, 3%; P less than .0005, chi 2). Neither the diagnosis, disease status, sex, nor the regimen altered the incidence of severe cerebellar toxicity (when corrected for age). A second course of high-dose cytosine arabinoside, administered to 62 patients, did not increase the incidence of severe cerebellar toxicity, which occurred in five (8%) of these patients. Two of the five patients had severe toxicity with the initial course. Of the 60 patients with no antecedent cerebellar dysfunction, three (5%) had severe toxicity with the second course: one of 41 patients were less than 50 years old; two of 19 patients were greater than or equal to 50 years. Since the occurrence of severe cerebellar dysfunction is greatly affected by age, reduced doses of high-dose cytosine arabinoside should be given to patients greater than 50 years old, and methods for reducing the cerebellar toxicity should be investigated in these patients.

Adolescent↗
PubMed1987

Bioavailability of high-dose oral leucovorin.

Fifteen adult subjects comprised the study group; 2 were colon cancer patients. Total leucovorin (citrovorum factor; CF) doses of 200, 400, 800, and 1600 mg were equally subdivided and administered at 0, 1, 2, and 3 hours. Three of the subjects were fasting and the other 12 were not. Quantitation of serum L-CF by Pediococcus cerevisiae and total reduced folates (TRF) by radio-assay were performed in 10 samples from each subject drawn over a 12-hour period after initiation of CF dosing. The mean serum levels of L-CF remained greater than 0.1 microM at 3 hours and the TRF 3.5 microM at 5 hours, respectively, after termination of CF dosing in all subjects treated at the 800- and 1600-mg dose schedule. At all CF dosage schedules employed, peak serum concentrations were reached within 4 and 6 hours after initiation of oral CF. Peak TRF concentrations at the 200-, 400-, 800-, and 1600-mg doses were 3.42 +/- 0.65, 4.05 +/- 1.04, 4.81 +/- 0.14, and 5.11 +/- 1.81 microM, respectively. Peak L-CF levels at 200, 400, 800, and 1600 were 0.15 +/- 0.11, 0.21 +/- 0.14, 0.23 +/- 0.11, and 0.34 +/- 0.16 microM. Based upon these observations, the following conclusions were reached: 1) no significant differences were observed in serum concentrations of folates between the 800- and 1600-mg dose schedules; 2) at these doses serum concentrations of L-CF and TRF were achieved that warrant a phase I investigation of high-dose oral CF with standard dose FUra in patients with advanced colorectal carcinoma.

Administration, Oral↗
PubMed1987

Evaluation of ethanol as an antiemetic in patients receiving cisplatin.

Nausea and vomiting are common complications of cisplatin chemotherapy. Patients with a history of chronic, heavy alcohol intake experience less nausea and vomiting from cisplatin than do those who are not heavy drinkers. Four patients being treated with cisplatin who had not obtained satisfactory control of nausea and vomiting with high-dose metoclopramide were given intravenous ethanol to alleviate their symptoms. In each case, the control of nausea and vomiting was inferior to that previously achieved with metoclopramide. It is concluded that acute ethanol administration has no clinically significant antiemetic effect in patients receiving cisplatin.

Cisplatin↗
PubMed1986

Treatment of advanced stage mycosis fungoides with bleomycin, doxorubicin, and methotrexate with topical nitrogen mustard (BAM-M).

Ten patients with advanced stage (TNM IIB-IVB) mycosis fungoides were treated with a combination chemotherapy program consisting of bleomycin and methotrexate weekly, doxorubicin every 3 weeks, and topical nitrogen mustard daily (BAM-M). Seven patients obtained histologically documented complete remissions ranging from 4 to 105+ months in duration. Median survival is 16.5+ months. Three patients in whom splenomegaly was detected during their staging evaluation underwent splenectomy. These three patients have had unmaintained disease-free survivals of 36+, 100+, and 105+ months. This study indicates that BAM-M is effective therapy for advanced stage mycosis fungoides and suggests that the therapeutic role of splenectomy should be evaluated further.

Adult↗
PubMed1986

Hypomagnesemia and renal magnesium wasting in patients treated with cisplatin.

Cisplatin (cis-diamminedichloroplatinum II), a chemotherapeutic agent used against epithelial neoplasms, is known to cause hypomagnesemia and renal magnesium wasting. In order to further characterize the effect of multiple doses of this drug upon serum magnesium levels and renal magnesium handling, we prospectively studied 28 patients who received a total of 82 doses of cisplatin. All patients developed hypomagnesemia that was dose-related (r = .66, P less than .001, n = 101); the lowest serum magnesium level reached in individual patients ranged from 0.3 to 1.7 mg/dL. Renal magnesium wasting was documented in 19 patients, with urinary fractional excretion of magnesium ranging from 2.9% to 22.3% despite serum magnesium levels of greater than or equal to 1.5 mg/dL. Evidence of renal tubular injury (renal tubular epithelial cells or tubular cell casts) was detected in 47 of 47 urine sediment examinations performed two to four days after cisplatin administration. There was no clear evidence that cisplatin caused defects in renal handling of electrolytes other than magnesium; in fact, 16 of the 28 patients demonstrated avid renal reabsorption of one or more other electrolytes despite significant magnesium wasting. We conclude that cisplatin alters renal tubular handling of magnesium, resulting in significant prolonged dose-related hypomagnesemia.

Adult↗
PubMed1986

Mixed small cell and non-small cell lung cancer.

Seventeen (10 percent) of 176 patients with small-cell carcinoma of the lung seen at this hospital since 1976 proved to have mixed small-cell and non-small-cell tumors. The presence of a mixed lung cancer was established prior to chemotherapy or irradiation in nine patients. Eight were initially diagnosed as pure small-cell carcinoma but proved to have a mixed tumor at either surgery or autopsy. Of the 17 patients, eight received chemotherapy, and four had a partial response. Six of the 40 autopsies performed on patients with small-cell lung cancer demonstrated intrathoracic tumor which was histologically mixed. Extrathoracic metastases in these patients were heterogeneous and included pure small-cell, pure non-small-cell, and mixed histologic type. We conclude that mixed small-cell and non-small-cell lung cancers are relatively frequent and carry important prognostic and therapeutic implications. Clinical management of patients with small-cell lung cancer should therefore be flexible and tailored to the potential for histologic diversity. Mixed lung cancer in previously untreated patients suggests a common endodermal origin for small-cell and non-small-cell pulmonary tumors.

Adult↗
PubMed1986

Chemoradiotherapy as initial management in patients with squamous cell carcinoma of the head and neck.

Thirty-nine previously untreated or minimally treated patients with squamous cell carcinoma of the head and neck were entered onto a chemoradiotherapy protocol employing multiple courses of simultaneous radiation therapy, cisplatin, and a 4-day 5-FU infusion. Thirty-eight patients were evaluable for response and toxicity. Twenty-three patients underwent surgical resection midway through this therapy and 11 (48%) were pathologically free of disease. Thirty-five of the 38 patients (92%) were ultimately rendered disease-free by this combined modality protocol. Thirty-one patients remain disease-free, with a projected 2-year disease-free survival of 74%. Although the treatment-associated mucositis and myelo-suppression were significant, this chemoradiotherapeutic approach is promising and merits further study.

Actuarial Analysis↗
PubMed1985

High-dose cytosine arabinoside in previously treated patients with poor-prognosis non-Hodgkin's lymphoma.

Fourteen previously treated patients with relapsed or refractory poor-prognosis non-Hodgkin's lymphoma were given chemotherapy regimens containing high doses of cytosine arabinoside alone (seven patients) or with an anthracycline or amsacrine (seven patients). Five patients achieved a complete remission and two patients had a partial remission. The durations of remission, however, were short (median, 3 months; range, 2-6 months). Toxicities included conjunctivitis, photophobia, stomatitis, dermatitis, cerebellar dysfunction, diarrhea, nausea, vomiting, liver dysfunction, and severe myelosuppression. Recovery of an absolute granulocyte count greater than 500/microliter and an untransfused platelet count greater than 20,000/microliter required a median of 31 (range, 28-35) and 30 (range, 27-43) days, respectively. Six patients died with recurrent or residual disease before bone marrow recovery. Younger age, good performance status, and a previous complete remission were predictive of a good response. High-dose cytosine arabinoside has major myelotoxicity but significant activity in some patients with poor-prognosis non-Hodgkin's lymphoma.

Adolescent↗
PubMed1985

Bone marrow morphologic changes after combination chemotherapy including VP-16.

Bone marrow aspirates and biopsy specimens were examined from seven patients with small cell lung cancer. All patients had received recent combination chemotherapy including VP-16. No correlation between marrow biopsy cellularity and hematologic toxicity could be established. However, an unusual combination of morphologic changes was seen. This included an initial rapid increase in the M:E ratio, interference with cell division, and eventual cell death. There was little evidence of mitotic arrest or megaloblastosis. These changes are consistent with the known mechanism of action of VP-16, the only agent given to all patients. The small sample size and the unknown contributions of the other cytotoxic agents administered allow only limited conclusions.

Antineoplastic Combined Chemotherapy Protocols↗