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Biomedical subjects

D L Trump

Publications and source records attributed to D L Trump.

At least 109 records · Page 6Linked to original sources
PubMed1987

Phase I study of taxol administered as a short i.v. infusion daily for 5 days.

Taxol inhibits cell division by promoting the assembly and stabilization of microtubules. This report describes the results of a phase I trial of taxol administered as a short iv infusion daily for 5 days every 4 weeks. Sixteen patients with refractory malignancy received 21 courses of taxol at five doses between 5 and 40 mg/m2/day X 5. The first nine patients received taxol as a 60-minute infusion. Two patients experienced anaphylactoid reactions, one at the 5-mg/m2/day and the second at the 15-mg/m2/day X 5 dose levels. These reactions were characterized by facial flushing, tachypnea, and hypotension within several minutes of drug administration. These anaphylactoid reactions occurred on the first day of treatment in the first patient and on the first day of the second course in the second patient. These reactions may be related to the rapid administration of the polyoxyethylated castor oil (Cremophor EL) vehicle in which taxol is formulated. No anaphylactoid reactions were observed in the seven patients who received taxol as a 6-hour infusion with antihistamine and prednisone premedication. Dose-related myelosuppression was seen; leukopenia (wbc count less than 1000/mm3) and granulocytopenia (granulocytes less than or equal to 200/mm3) occurred on Days 8 and 9 in two of two patients treated at the 40 mg/m2/day X 5 level. Thrombocytopenia was mild, with a platelet nadir of 87,000-95,000/mm3 at the highest dose level. Premedication with glucocorticoids and antihistamines coupled with a prolonged 6-hour infusion permitted taxol to be administered at 30 mg/m2/day X 5 safely without immediate life-threatening reactions.

Alkaloids↗
PubMed1987

High-dose lymphoblastoid interferon in advanced renal cell carcinoma: an Eastern Cooperative Oncology Group Study.

This report describes a phase II Eastern Cooperative Oncology Group (ECOG) study of high-dose lymphoblastoid interferon (IFN alpha-n1) in 39 patients with measurable, advanced renal cell carcinoma. The original treatment plan was 30 X 10(6) units/m2 (30 mU) of IFN alpha-n1 im daily X 10 days; treatments were repeated every 21 days. This dose and schedule proved intolerable, with none of seven patients able to complete greater than 10 days of therapy because of fever, lassitude, hepatic dysfunction, and myelosuppression. Patients were subsequently treated with the following regimen: 3 mU/m2 on Day 1; 5 mU/m2 on Day 2; 10 mU/m2 on Day 3; and 20 mU/m2 on Days 4-10. Thirty-three new patients received this regimen and two patients received this schedule after having received 30 mU/m2. Using this second regimen, 30% of the patients were able to complete two cycles of treatment without dose reduction or interruption. Five patients (13%) had partial response (ECOG criteria) of measurable tumor. Median time to response was 140 days. Responses were documented in lung metastases in four patients and in a pelvic soft tissue mass in the fifth. Response rates and survival times are similar to those seen in prior ECOG phase II trials in advanced renal cell carcinoma. Eight of 39 patients are still alive greater than 2 years after beginning therapy. Only two of these patients had had an objective response, however. Such prolonged survival is more frequent than has been seen in previous ECOG studies. The relative contribution of patient selection and interferon therapy to this survival is uncertain.

Aged↗
PubMed1986

Metastatic Leydig cell tumor of the testis. Report of three cases and review of the literature.

Metastatic Leydig cell carcinomas account for less than 0.2% of all testicular cancers, and may be associated with sex hormone production. Leydig cell carcinoma is relatively refractory to radiotherapy and chemotherapy, and median survival of patients with metastatic disease is less than 2 years. Presented are three cases of metastatic Leydig cell cancer, and a review of the literature pertaining to this rare tumor.

Adult↗
PubMed1986

Psychological distress among women with breast problems.

Visiting a physician for evaluation of a breast problem which could be cancer is often assumed to be a highly stressful experience. This study evaluates the degree of emotional distress in women about to undergo examination for signs or symptoms of breast disease. Three hundred twenty-two women who attended the Breast Problem Clinic of the Wisconsin Clinical Cancer Center were studied. Each patient completed standard self-administered psychologic tests to evaluate mood disturbance (Profile of Mood States [POMS]) and responsibility taken for overall health care (Health Locus of Control [HLCS]). Results of these tests were compared to control populations of normal college women and female psychiatric outpatients. The women seen in the Breast Problem Clinic were significantly less distressed on POMS subscales which measure depression, anger, fatigue, and confusion than both psychiatric outpatients and normal college women (P less than 0.001). A second group of 17 women who were seen in the hospital 24 to 48 hours before definitive breast cancer surgery were also studied. Women evaluated as inpatients before breast cancer surgery were more distressed than the women attending the outpatient clinic on most POMS subscales, but were not clearly different from normal college women. No differences between the groups were seen for the HLCS. These data indicate that emotional distress among women attending a breast problem clinic is not extraordinary, but that emotional distress heightens when the diagnosis of breast cancer is known.

Breast Neoplasms↗
PubMed1986

Phase I clinical trial and pharmacokinetics of carboplatin (NSC 241240) by single monthly 30-minute infusion.

Carboplatin (diammine [1,1-cyclobutanedicarboxylate(2-)-O,o']platinum) is a second generation platinum coordination complex. It has a spectrum of activity that is similar to that of cisplatin and is less nephrotoxic and emetogenic in experimental animals. Fifty-two 30-minute infusions of carboplatin were given to 20 evaluable patients with a variety of solid tumors. Maximum tolerated dose was 440 mg/m2. Thrombocytopenia (less than 100,000/mm3) occurred in six of seven patients; two patients experienced a leukocyte count less than 2000/mm3. Platelet and leukocyte count nadirs occurred on day 21. No nephrotoxicity was seen. Blood urea nitrogen, serum creatine levels, and creatinine clearances remained normal, and no consistent elevation of urinary beta 2-microglobulin, leucine aminopeptidase, or N-acetyl-beta-glucosaminidase occurred. Nausea and vomiting were mild to moderate. A single patient developed mild peripheral neuropathy. No auditory toxicity was noted. The recommended dose for Phase II studies is 400 mg/m2 every 28 days for good risk patients; heavily pretreated patients should receive 320 mg/m2.

Antineoplastic Agents↗
PubMed1986

Phase II evaluation of a combination of mitomycin C, vincristine, and cisplatin in advanced non-small cell lung cancer.

The combination treatment of mitomycin C (M), vincristine (V), and cisplatin (P) (MVP) in 63 patients with advanced non-small cell lung cancer (NSCLC) were evaluated for their potential synergistic cytotoxicity. The overall response rate was 43% (27/63); in the 54 eligible and evaluable patients, the response rate was 50% (27/54). Responses were observed in all cell types and disease sites. Cell type; performance status of 0, 1, or 2; sex; and age younger or older than 60 years did not significantly influence the response rate. However, patients with prior radiation had significantly more treatment failure than those without. The dose-limiting side effects in these 54 patients were myelosuppression (40%), pulmonary fibrosis (9%), peripheral neuropathy (6%), and intractable nausea and vomiting (4%). The degree of leukopenia (P less than 0.01) but not of thrombocytopenia increased significantly in patients who had received prior radiotherapy. One patient died of marked thrombocytopenia and one of fulminant hepatitis. Patients who responded lived significantly longer than those who did not (P less than 0.004). A majority of the responders (82%) also achieved symptomatic palliation. With appropriate dose modification and supportive care, MVP was tolerable. Further trials with this regimen or a modified version are worth consideration.

Adult↗
PubMed1986

Reversible increase in serum alpha-fetoprotein content associated with hepatic dysfunction during chemotherapy for seminoma.

Serial monitoring of the serum content of the beta subunit of human chorionic gonadotropin (beta hCG) and alpha-fetoprotein (alpha FP) is useful in the initial staging of germ cell tumors and assessing the response to treatment. An increase in either marker during or following treatment almost always heralds disease progression and indicates the need for additional therapy. We report two patients in whom substantial increases in the serum content of AFP occurred during chemotherapy for advanced seminoma. Hepatic dysfunction was present in both patients; in one patient, a chronic carrier of hepatitis B virus, the liver dysfunction was associated with reactivation of hepatitis B manifested by anicteric hepatitis and hepatitis B e antigen positivity. Marked tumor regression had occurred in both patients, and chemotherapy was discontinued in spite of the elevated alpha FP level. The alpha FP content in the serum gradually returned to normal, and hepatic dysfunction resolved. Both patients remain free of disease 15 and 17 months following the last chemotherapy treatment. These cases illustrate that hepatic dysfunction and alpha FP production may occur during chemotherapy and that increases in serum alpha FP content must be interpreted with caution since the elevated alpha FP level does not always indicate progression of germ cell tumors.

Adult↗
PubMed1985

Clinical features and natural history of intramedullary spinal cord metastasis.

Five cases of intramedullary spinal cord metastasis are presented and an additional 50 cases from the English language literature since 1960 are reviewed. Lung cancer and breast cancer were the most frequently occurring primary neoplasms, but a wide variety of solid tumors may cause intramedullary spinal cord metastasis. The presenting symptoms were pain and/or weakness. The neurologic status deteriorated rapidly in the majority of patients in a period to days to weeks. Progression to a cord hemisection syndrome or cord transection occurred in approximately half of the patients. The characteristic myelographic appearance of fusiform swelling of the cord was seen in one third of the patients, but the myelogram was normal in 42%. Plain radiographs of the spine showed no evidence of metastatic disease in three fourths of cases. The cerebrospinal fluid protein level was frequently elevated, but results of cytologic studies were usually negative. High-resolution computer-assisted tomographic scanning may show intramedullary metastases. Radiation therapy combined with corticosteroid administration offers the only effective palliation. The recognition of intramedullary spinal cord metastasis is an ominous finding. Intramedullary spinal cord metastasis generally occurred in the setting of widespread systemic and intracranial disease, but occasionally was the only site of relapse. More than 80% of patients died within 3 months. Heightened awareness of this entity may lead to early diagnosis at a stage when neurologic deficits are reversible and, it is hoped, more effective palliation can be achieved.

Adult↗
PubMed1985

Modulation of 5-iodo-2'-deoxyuridine metabolism and cytotoxicity in human bladder cancer cells by fluoropyrimidines.

Iododeoxyuridine (IdUrd) potentiated the lethal but not the growth inhibitory properties of fluorouracil (FUra) and fluorodeoxyuridine (FdUrd) in human bladder cancer cells (T24). The rate of incorporation of IdUrd into DNA was enhanced by both fluoropyrimidines, but to a significantly greater extent by FdUrd. Both inhibition of iododeoxyridylate dehalogenation and the depletion of thymidine triphosphate pools contributed to the increased incorporation rate. Inhibition of dehalogenation accounted for 67% of the observed stimulation in the case of FUra, but only 37% of the increase produced by FdUrd. The depletion of dTTP pools, both in the presence and absence of IdUrd, was greater after FdUrd than FUra exposure. The observed increase in the rate of incorporation of IdUrd appears to account for the enhanced toxicity seen with FdUrd, but other factors may be involved in the case of FUra. Since FUra and IdUrd appear to be mutually potentiating and do not share a dependence on thymidine kinase activity, this drug combination warrants further investigation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Etoposide and very high dose cisplatin: salvage therapy for patients with advanced germ cell neoplasms.

Twelve patients with refractory germ cell tumors were treated with etoposide (VP16) (100 g/m2/day X 5) and very high dose cisplatin (VHD-CDDP) (40 mg/m2/day X 5) every 28 days. All patients had progressed or relapsed after therapy with vinblastine (0.15 mg/kg/day X 2), CDDP (20 mg/m2/day X 5), and bleomycin (30 units/week). Thirty-three cycles of VP16 plus VHD-CDDP were administered. Five patients achieved complete response (two with chemotherapy only, two with chemotherapy + surgery, and one with chemotherapy + irradiation), five achieved partial response (two continue therapy), and two had disease progression. Only one patient achieved prolonged complete response (24+ months). Myelosuppression (median wbc count nadir, 1200/mm3; median platelet count nadir, 18,500/mm3), neurotoxicity (five patients with diminished hearing and six with substantial peripheral neuropathy), and hypomagnesemia (21 of 22 courses; magnesium, less than 1.5 mg/dl) were the dominant toxic effects. No important nephrotoxicity was seen (median maximum creatinine, 1.2 mg/dl; range, 0.8-2.2). VP16 plus VHD-CDDP is safe and tolerable and may provide a non-cross-resistant alternative to vinblastine, CDDP, and bleomycin.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Mitomycin for patients who have failed on thiotepa. The National Bladder Cancer Group.

The National Bladder Cancer Group undertook a study to determine the effectiveness and toxicity of mitomycin in patients who failed on thiotepa. A total of 117 patients with residual superficial transitional cell bladder cancer (Ta, T1, Tis) who had previously failed on intravesical thiotepa were treated with 40 mg of mitomycin instilled intravesically weekly for eight weeks. Four to six weeks after the last treatment, tumor response was evaluated by cystoscopy, biopsy of the site of the index lesion, and cytology. In 57 patients (48.7%), visible tumor had been ablated. Results of cystoscopy, biopsy, and cytology were negative in 32 (27.4%) patients. Eleven patients (9.4%) had no visible tumor and negative cytology unconfirmed by biopsy. In 14 patients (12%) who had complete destruction of the tumor at cystoscopy, and biopsy specimen was negative for tumor, cytology was positive, indicating a partial response. Six patients (5.1%) withdrew from the study before the first evaluation because of local toxicity (cystitis).

Administration, Topical↗
PubMed1985

Phase I clinical study with pharmacokinetic analysis of 2-beta-D-ribofuranosylthiazole-4-carboxamide (NSC 286193) administered as a five-day infusion.

A Phase I trial of 2-beta-D-ribofuranosylthiazole-4-carboxamide (NSC 286193, tiazofurin) was conducted using a 5-day continuous infusion schedule. Twenty-four patients with advanced cancer were entered on this trial. Dose levels ranged from 360 to 2350 mg/sq m/day for 5 days. Neurotoxicity was dose limiting and occurred in six patients. Neurotoxicity was expressed as confusion, lethargy, or obtundation and was associated with focal neurological deficits in four of six patients: hemiparesis, three; cortical blindness and bilateral upper extremity weakness, one. Neurotoxicity was not clearly dose related, occurring at 900 mg/sq m/day for 5 days (two patients), 1100 mg/sq m/day for 5 days (two patients), 1850 mg/sq m/day for 5 days, and 2350 mg/sq m/day for 5 days (one patient each). Other toxicities seen were myelosuppression, desquamation of palms and soles, malar erythema, and hyperpigmentation, stomatitis, chest pain, drug fever, and increased serum creatine phosphokinase. Administered drug [71.5 +/- 11.2% (SE)] was recovered intact in the urine within 24 h of administration. Terminal-phase mean harmonic half-life was 8.0 h. The unpredictable neurotoxicity seen following continuous infusion therapy with tiazofurin suggests that Phase II trials of this schedule are not indicated until better understanding of the biochemical effects of tiazofurin is achieved.

Adult↗
PubMed1985

Massive skeletal muscle invasion by lymphoma.

Three patients had diffuse enlargement of skeletal muscle of the thigh as the result of infiltration by diffuse large-cell lymphoma. One case presented de novo as diffuse lymphoma, but the other two had previous diagnoses of nodular lymphoma and Hodgkin's disease. Computed tomographic scanning disclosed an enhancing mass in the thigh with infiltration of skeletal muscle groups; abnormal medullary cavities were noted in the adjacent long bones. Muscle biopsy established the diagnosis in two of the patients.

Adult↗
PubMed1984

Metastatic carcinoma involving the testis. Clinical and pathologic distinction from primary testicular neoplasms.

Metastatic carcinoma to the testis is unusual. There are only seven previously reported cases in which a testicular mass was the first clinical manifestation of an underlying malignancy. The authors review 127 cases in which the testis was involved by metastatic carcinoma, and describe an additional two patients in whom a malignant testicular mass was the presenting sign of an underlying nontesticular carcinoma. The tumors most commonly reported to metastasize to the testis are: prostate (45 cases), lung (25 cases), melanoma (12 cases), colon (11 cases), kidney (10 cases), stomach (6 cases), and pancreas (5 cases). Neuroblastoma, retinoblastoma, carcinoid tumor, and cancers of the bile duct, ureter, bladder, salivary gland, and thyroid have also involved the testis secondarily. Nineteen patients (15%) had bilateral testicular metastases. Patients with secondary testicular neoplasms were older in general than those with germ cell tumors (mean, 55 years; median, 57 years). Histologically, the presence of extensive lymphatic and vascular invasion and an interstitial pattern, in which the seminiferous tubules are spared, is suggestive of a metastasis. In four of the nine cases (44%) in which testicular enlargement was the first manifestation of an underlying carcinoma the correct pathologic diagnosis was initially missed. Serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) are occasionally elevated in patients with nontesticular primary tumors, but markedly elevated levels in young patients suggest a nonseminomatous germ cell tumor, as does positive immunoperoxidase staining for AFP and HCG.

Adolescent↗