摘要:

Twenty-five patients with metastatic malignant melanoma were treated with isotretinoin (13-cis-retinoic acid) orally at 1 mg/kg daily and recombinant interferon alfa-2a (IFN-α) subcutaneously at 3 million units daily for 16–48 weeks. Therapy was well tolerated; fatigue and hyperlipidemia were the most frequent dose-limiting toxicity and necessitated dose reductions in 14 patients. Two patients achieved a complete response, and 3 responded partially for a total response rate of 20% (95% confidence interval: 4–36%). Responses occurred primarily in patients with limited tumor burden and disease confined to the skin and lymph nodes. Significant elevations in peripheral blood 2′-5′-oligoadenylate synthetase activity and natural killer activity were observed with therapy. The magnitude of these changes, however, was not predictive of response. Biopsy specimens of two responding lesions showed extensive necrosis of tumor. One specimen showed large aggregates of melanophages in association with tumor. The combination of isotretinoin and IFN-αis an active, easily administered regimen with acceptable toxicity for metastatic malignant melanoma

ISSN:0735-7907    

DOI:10.3109/07357909609012154

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

In an attempt to reestablish normal hematopoiesis in symptomatic myelodysplasia (MDS) and to show the tolerability of a combination treatment of low-dose cytosine arabinoside (LD AraC) and interleukin-3 (IL-3), we treated 31 patients (pts., median age 65 years) who had more than 10% blasts in the bone marrow (BM) and hematopoietic failure with LD AraC (2<10 mg/m2sc, day 1–14) plus IL-3 (once daily sc, day 8–21) at different dose steps (1.0, 2.5, 5.0, and 10.0μg/kg body weight). The numbers of' each 21-day cycle varied between 1 (3 pts.), 2 (6 pts.), 3 (8 pts.), 4 (1 pt.), 5 (5 pts.), and 6 (8 pts.), in total 116 cycles on an outpatient basis. Subjective tolerability was good in 20 cases (65%). Toxicities were fever (29 pts.), flu-like symptoms (17pts.), infections (15 pts.), hepatic toxicity (10 pts.), and skin reactions (8 pts.). Overall response was seen in 13 cases (42%) with 5 complete responses (CR), while 10 pts. had stable disease (SD), 5 progressed (2 to acute leukemia), 2 were considered toxic deaths, and 1 died due to the disease. Median survival is 18 months, progression-free survival is 12.5 months (18.0 months in responding pts.), with an actuarial follow-up of 31 months. The data from this phase I/II study show that a combination of LD-AraC and IL-3 is well tolerated and that stable responses can be achieved in MDS by means of an easy outpatient therapy.

ISSN:0735-7907    

DOI:10.3109/07357909609012155

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Platelet function in 12 cancer patients was studied sequentially over 97 hr of interleukin-6 (IL-6) daily bolus or continuous infusion (C.I.) therapy. During this period, enhanced ex vivo agonist-induced platelet maximum aggregation (MA) was paralleled by an increase in plasma levels of TXB2and PF4 as measured by RIA and ELISA, respectively. Platelet-rich plasma (PRP) specimens from bolus IL-6-treated patients demonstrated an increased incorporation of actin-binding protein and myosin in the cytoskeletal core (triton insoluble residue) as shown by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) in comparison to control specimens. Similarly, the integrin glycoprotein IIIa (GPIIIa) was also observed to be retained into the cytoskeleton by immunoblot. A significant decrease in hypotonic shock response (HSR) was observed over 87 hr of treatment in IL-6 C.I. patients, whereas in IL-6 bolus patients, a significant increase in HSR occurred immediately after the bolus, which was followed by a significant decrease in HSR after 23 hr. These results suggest that IL-6 alters platelet function in vivo.

ISSN:0735-7907    

DOI:10.3109/07357909609012156

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Discrimination in the delivery of health care, based on the age of the patient, is attracting increased attention. We investigated this problem by studying possible age-related delay in diagnosis in patients treated for glioblastoma multiforme (GBM). A total of 213 charts of patients with GBM seen from 1972 to 1992 were evaluated for type and duration of symptom, with 204 charts having sufficient data to be analyzed. The mean and median duration of symptoms for the entire group was 48.9 and 28 days, respectively. No age-related difference in duration of symptoms was noted. In light of the increasing incidence of GBM in patients above 60 years of age, further investigation of other possible areas of age discrimination in patients with GBM is warranted.

ISSN:0735-7907    

DOI:10.3109/07357909609012157

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Amonafide (A) demonstrates dose-related increases in area under the curve (AUC) and Cmax values. Total body clearance for A (ranging from 44.2 to 53.8 L/hr/m2) is relatively constant within the dosing range of this study. The dose-related increase of AUC was also observed for the two identified metabolites, acetylamonafide (AA) and noramonafide (NA). A and NA plasma data could be described by a four-compartmental model (two compartments for A, one compartment each for NA and AA). The fitting for NA was poor owing to its low plasma concentration. The terminal half-lives for A, NA, and AA were in the range of 3–6 hr. No cumulative accumulation of parent compound or metabolites was detected after daily administration. The concentrations of A, NA, and AA 24 hr after dosing were either below or very close to the quantitative limits of the assay. Polymorphic disposition of A was confirmed by a frequency distribution of AUC value versus dose plot

ISSN:0735-7907    

DOI:10.3109/07357909609012158

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Vitamin D3D3) has been found to exert varied pharmacological actions including restriction of cell growth of a number of malignant cell lines in vitro and inhibition of the promotion of chemical carcinogenesis in mouse skin. In an attempt to confirm the efficacy of D3as an antineoplastic agent, the present investigation aims at characterizing the importance of D3in modulating hepatic drug metabolizing enzymes, namely, cytosolic glutathione S-transferase (GSHT), microsomal UDP glucuronyl transferase (UDPGT), and cytochrome P-450, which have been reported by us in recent literature as significant neoplastic markers in mice bearing Dalton's lymphoma (DL). Results show that D3causes a 150% elevation of GSHT activity and the maintenance of normal, near-control UDPGT activity and cytochrome P-450 content, up to almost 30 days following tumor transplantation, along with bringing about a twofold increase in survival of the host mice. In conclusion, we confirm the definite and significant antitumorigenic role of D3and its involvement with the discussed hepatic tumor markers in monitoring the processes that lead to cell survival

ISSN:0735-7907    

DOI:10.3109/07357909609012159

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Small cell carcinoma of the pancreas is a very rare malignancy with 18 cases reported in the literature, of which only 3 were treated with chemotherapy. A 52-year-old man was diagnosed with small cell carcinoma originating in the head of the pancreas and invading the duodenum. He was treated with a similar approach as for localized small cell lung cancer, with six cycles of combination chemotherapy and local radiotherapy, and went into complete remission. After 3 months, he developed liver metastases along with an enlarged left supraclavicular lymph node. He was treated with two cycles of CVA, but developed lung metastases and was treated with ifosfamide/mesna. However, his overall condition deteriorated and hospice care was instituted until the patient's demise. The patient survived 14 months following diagnosis, significantly longer than the 15 reported patients with small cell pancreatic carcinomas not treated with chemotherapy. Combination chemotherapy and radiation therapy as is utilized for small cell lung cancer appear to be beneficial for small cell carcinoma of the pancreas.

ISSN:0735-7907    

DOI:10.3109/07357909609012160

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

ISSN:0735-7907    

DOI:10.3109/07357909609012161

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

ISSN:0735-7907    

DOI:10.3109/07357909609012162

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

ISSN:0735-7907    

DOI:10.3109/07357909609012163

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor