Phase II trial of gallium nitrate,amonafide and teniposide in metastatic non-small cell lung cancer

Summary Fifty-five patients with metastatic non-small cell lung cancer (NSCLC) were entered into this phase II randomized study for evaluating three new agents: gallium nitrate, amonafide and teniposide. The patients had to have ECOG performance status 0 or 1, no prior chemotherapy, and adequate hematological, hepatic and renal functions. Forty-seven patients were eligible and evaluable. Fourteen were randomized to receive gallium nitrate, 18 to amonafide and 15 to teniposide. Seventy-four percent of eligible patients were male. The majority of patients (89%) had an ECOG performance status 1. ECOG grade 4 toxicity occurred twice in patients on gallium nitrate, seven times on amonafide and 18 times on teniposide. The cause of death was attributed to amonafide in one patient (from sepsis) and to teniposide in two patients (due to infection and leukopenia). There was no objective response in all the patients entered. The overall survival times ranged from 2 weeks to 156 weeks with a median of 23 weeks. There were no survival differences among the three treatment arms. We conclude that gallium nitrate, amonafide and teniposide are inactive in metastatic NSCLC and do not warrant any further testing in this disease.The contents of this study is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute.     

Comparison of indium-111 octreotide and thallium-201 scintigraphy in patients mammographically suspected of having breast cancer: Preliminary results

Indium-111 octreotide and thallium-201 scintigraphic studies were compared in 21 patients (16 with palpable and five with non-palpable lesions) suspected of having breast malignancies on the basis of mammography. Early (15 min) and late (3 h)²⁰¹Tl (111 MBq) and 4-h and 24-h¹¹¹In-octreotide (111–148 MBq) static planar anterior images (matrix 256×256) were obtained on separate days. Images were evaluated both visually and quantitatively. Biopsy was performed following the imaging studies. Histopathology revealed 17 breast carcinomas (15 cases of invasive ductal carcinoma, one mucinous adenocarcinoma and one intraductal carcinoma) and four benign breast lesions (two fibroadenomas, one abscess and one case of fat necrosis). The means histopathologcial tumour size (mean largest diameter) was 3.38±1.9 cm.¹¹¹In-octreotide detected 16 of the 17 breast cancers (94%) while²⁰¹Tl detected 13 of them (76%). Both¹¹¹In-octreotide and²⁰¹Tl missed one nonpalpable carcinoma showing only an isolated cluster of microcalcifications on mammography. The smallest tumour size detected by both agents 1.5×1.5 cm. Of the four benign lesions, only the breast abscess revealed both²⁰¹Tl and¹¹¹In-octreotide uptake.¹¹¹In-octreotide scan also showed tracer uptake in five of the six patients with histologically proven axillary metastases, while four of these six patients showed²⁰¹Tl uptake. The tumour/background (T/B) ratios of late¹¹¹In-octreotide and²⁰¹Tl images were 1.71±0.38 and 1.46±0.30 respectively (P=0.039). In this preliminary study,¹¹¹In-octreotide yielded more favourable results than²⁰¹Tl in the detection of breast carcinomas. However, the diagnostic efficacy of¹¹¹In-octreotide imaging needs to be investigated in larger patient series.     

Mycotic aneurysm of the aorta: MRI and MRA features

Mycotic aneurysms of the abdominal aorta are potentially fatal but uncommon. We report the MRI and MRA features of an abdominal aortic mycotic aneurysm in a patient who presented with nonspecific low back pain. By delineating the saccular nature of the aneurysm and identifying the coexistence of vertebral enhancement, MRI was crucial for the final diagnosis. A potential pitfall of contrast-enhanced MRA is also demonstrated.     

Intensive chemotherapy for peripheral T-cell lymphomas.

Forty-two patients with previously untreated peripheral T-cell lymphomas (PTCL) were treated with an intensive chemotherapy protocol. Either the BACOP or the m-BACOD regimen was used for induction. Patients achieving complete clinical remission after three courses were given intensive consolidation and maintenance chemotherapy similar to the L10/L17M protocol designed by the Memorial Sloan-Kettering Group for acute lymphoblastic leukemia and lymphoblastic lymphoma. There were 27 (64 per cent) males and 15 (36 per cent) females. The median age was 54 years (mean 53, range 15 to 68). Seven of them (17 per cent) had stage I disease, four (10 per cent) stage II, seven (17 per cent) stage III and 24 (57 per cent) stage IV. Eighteen patients (43 per cent) had B symptoms and four (10 per cent) had bulky disease. According to the Working Formulation, the histology was diffuse mixed in 16 patients (38 per cent), diffuse large cell in 18 (43 per cent), diffuse immunoblastic in four (10 per cent) and unclassifiable in four (10 per cent). According to a modified Japanese Lymphoma Study Group's classification, the histology in 24 patients (57 per cent) was the pleomorphic type, in 13 (31 per cent) immunoblastic-lymphadenopathy-like (IBL-like), and in five (12 per cent) unclassifiable. The overall complete remission rate was 67 per cent. Twenty-five per cent of the complete responders relapsed and the DFS of the CR patients was 62 per cent at three years. The overall survival of all patients at three years was 52 per cent. Patients with stage I, II and III disease had significantly better CR rate (100 per cent versus 42 per cent, p = 0.001) and overall survival (82 per cent versus 35 per cent at three years, p = 0.01) than those with stage IV disease but the relapse rate and DFS of CR patients were similar. This study shows that the prognosis of patients with PTCL can be improved by intensive therapy.     

Incisional healing in rats treated with diethyl maleate

Diethyl maleate (DEM) which binds and thus depletes tissue glutathione levels was used to aggravate the injury and to determine its effect on incisional healing. A 5 cm dorsal midline skin incision was performed on 40 albino Wistar rats in two groups and then closed by interrupted sutures. Groups received 0.9% NaCl and DEM at a dosage of 1 mg/kg/day intraperitoneally for seven days, respectively. On postoperative days 7 and 14, histopathological assessment and tensile strengths were measured. The DEM treated group had a marked inflammation with poorly defined collagen formation and the tensile strength measurements revealed a significant decrease (p <0.001) on the 7t day. On the other hand, the first group showed better collagenization and a lesser degree of inflammation. However, on the 14th day, there was no noticeable histopathological difference between the two groups; but, tensile strength values of the second group were still lower (p <0.05). In this animal model, DEM postponed the healing process and reduced the tensile strength.     

Expression of human mu or alpha class glutathione S-transferases in stably transfected human MCF-7 breast cancer cells: effect on cellular sensitivity to cytotoxic agents.

Increased expression of certain glutathione S-transferase (GST) isoenzymes has frequently been associated with the development of resistance to alkylating agents and other classes of antineoplastic drugs in drug-selected cell lines. The question arises whether this phenomenon is causal or is a stress-induced response associated with drug resistance in these cell lines. We have constructed mammalian expression vectors containing the human GST mu and GST alpha 2 (Ha2) cDNAs and stably transfected them into the human breast cancer cell line MCF-7. Whereas the parental and pSV2neo-transfected cell lines display low GST activity, three individual transfected clones were identified in each group that expressed either GST mu or GST alpha 2. The range of GST activities was similar to those observed in cells selected for anticancer drug resistance. The GST mu specific activities were 56, 150, and 340 mlU/mg, compared with 10 mlU/mg of endogenous GST mu in control lines. Specific activities in GST alpha 2-transfected clones were 17, 28, and 52 mlU/mg, compared with no detectable alpha class GST in control lines. These clonal lines and the parental and pSV2neo-transfected control lines were tested for sensitivity to antineoplastic agents and other cytotoxic compounds. The clones with the highest activity in each group were 1.7-fold (GST alpha 2) to 2.1-fold (GST mu) resistant to the toxic effects of ethacrynic acid, a known substrate for GSTs. However, the GST-transfected cell lines were not resistant to doxorubicin, L-phenylalanine mustard, bis(2-chloroethyl)-1-nitrosourea, cisplatin, chlorambucil, or the GST substrates 1-chloro-2,4-dinitrobenzene or tert-butyl hydroperoxide. Thus, although L-phenylalanine mustard, bis(2-chloroethyl)-1-nitrosourea, chlorambucil, tert-butyl hydroperoxide, and 1-chloro-2,4-dinitrobenzene are known to be metabolized by glutathione-dependent GST-catalyzed reactions, there was no protection against any of these agents in MCF-7 cell lines overexpressing GST mu or GST alpha 2. We conclude that, at the levels of GST obtained in this transfection model system, overexpression of GST mu or GST alpha 2 is not by itself sufficient to confer resistance to these anticancer agents. These studies do not exclude the possibility that GST may be a marker of drug resistance or that other gene products not expressed in MCF-7 cells might cooperate with GST to confer drug resistance.     

Restriction fragment length polymorphism analysis to study the genetic origin of complete hydatidiform mole.

To determine the genetic origin of the complete hydatidiform mole, 20 abnormal pregnancies were studied with restriction fragment length polymorphism with five genomic probes: EJ 6.6, beta-globin gene, 3'alpha-hypervariable region, J-Bir, and St14. In the 12 cases of molar pregnancy, pure paternal origin was proved in 11 cases, but both maternal and paternal inheritance were shown in only one case. In the cases with pure paternal origin, all of the restriction fragment length polymorphisms were homozygous, although those of the fathers were heterozygous at 15 loci. In the four cases that mimicked hydatidiform mole but were diagnosed as hydropic change of villi, both paternal and maternal inheritance were noted. In the four pregnancies with blighted ovum, both paternal and maternal inheritance were shown in three cases; and in one case with a balanced translocation between chromosomes 13 and 14, only paternal inheritance was noted. This study showed that most of the complete hydatidiform moles were caused by fertilization of an empty egg by a duplicated haploid sperm, but rare exceptions may exist.     

Modeling two dimensions of patient satisfaction: a panel study.

Measurement of patient satisfaction is an essential part of health outcome assessment. The purpose of this study is (a) to compare the stability of an aggregate summary measure and two separate summary measures of patient satisfaction; and, (b) to examine causal effects between two separate summary measures at two points in time. Data were collected from 1,451 Medicare HMO beneficiaries. In conclusion, (a) separate summary measures are recommended for constructing the measure of patient satisfaction and (b) moderate causal relationships and cross-lagged effects between the patient satisfaction measures of qualify of care and access to care were found.