Biomedical subjects

J A Levi

Publications and source records attributed to J A Levi.

At least 37 records · Page 2Linked to original sources

PubMed1990

Current status of treatment for breast cancer.

Recent developments in the treatment of early stage breast cancer include mature data from randomised trials that indicate limited surgery with breast irradiation provide comparable survival to total or radical mastectomy. For patients undergoing radical mastectomy while post-operative radiotherapy should not be routine, when more than four axillary lymph nodes are involved at surgery or the primary tumour involves the medial quadrants, then local recurrence rates are significantly reduced by this radiotherapy. Overview statistical metanalyses of data from adjuvant therapy trials has confirmed that cyclophosphamide, methotrexate and 5-fluorouracil chemotherapy reduced the risk of death by 24 +/- 6% compared to controls for premenopausal women. Whereas, administration of tamoxifen for more than one year to postmenopausal women with positive axillary lymph nodes and positive hormone receptor levels resulted in a 18 +/- 4% reduction in mortality. Similar adjuvant treatments in women with negative axillary lymph nodes but other adverse prognostic factors improves disease-free but not as yet overall survival. In advanced disease, the success of hormone manipulation is dependant on the presence and amount of oestrogen and progesterone receptor protein in either the primary breast tumour or a biopsied metastasis. If a response is achieved, this will be complete in 5-20% of patients with a median survival in excess of 18 months for responding patients and 25% remaining alive and disease-free beyond 30 months. Combination chemotherapy for patients with negative hormone receptors or aggressive disease achieve response in 50-60% of patients. Current activity to improve the therapeutic index of chemotherapy include less toxic analogs, priming hormones and high dose chemotherapy.

Breast Neoplasms↗

PubMed1989

Dose intensity and outcome with combination chemotherapy for germ cell carcinoma. Australasian Germ Cell Trial Group.

Two hundred and fifty-three patients with advanced stage germ cell carcinoma received induction chemotherapy with vinblastine, bleomycin and cisplatin, sometimes with subsequent surgical resection of residual masses. Overall, 191 patients (76%) achieved complete remission or no evidence of disease after surgery (CR + NED). With 64 months median follow-up only 24 patients have relapsed (13%) and 68% of all patients treated are long-term survivors and 84% of patients entering CR + NED are alive. Toxicity with this chemotherapy was considerable, including seven deaths from leukopenia and septicaemia and eight deaths from bleomycin lung toxicity. Dose reductions or omissions of the drug from the treatment programme was necessary with cisplatin in 8% of patients, with vinblastine in 37% and with bleomycin in 35% of patients. Analysis of these alterations in dose intensity for each drug revealed that initial treatment response and subsequent survival were not compromised by reductions in intended doses of drug administered for either vinblastine or bleomycin. Too few patients had dose reductions of cisplatin for meaningful analysis. This apparent lack of major dose-response effect for either vinblastine or bleomycin in the present treatment programme for germ cell carcinoma has prompted the initiation of a randomized study to determine whether deletion of bleomycin from treatment for patients with good prognostic pretreatment characteristics improves the therapeutic index of this very successful therapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1989

Double-blind randomized cross-over trial of dexamethasone and prochlorperazine as anti-emetics for cancer chemotherapy.

A double-blind randomized cross-over trial of dexamethasone and prochlorperazine as adjunctive anti-emetics with cancer chemotherapy was undertaken. The drugs were compared for cisplatin, doxorubicin and several other chemotherapy regimens. A total of 44 eligible patients were analysed. Assessment was made by questionnaire answered by the patient 24 h after the chemotherapy. The parameters compared were period of time for nausea and vomiting, number of vomiting episodes, degree of somnolence and insomnia and overall preference. In all cases there was no significant difference for either drug in its ability to suppress emetic effects. Neither drug gave adequate protection against cisplatin-containing regimens. We conclude that dexamethasone alone is equivalent to the more standard dopamine antagonists.

Adult↗

PubMed1988

Cisplatin plus VP 16-213 in advanced ovarian carcinoma.

Thirty-five patients with advanced epithelial ovarian carcinoma (24 untreated, 11 previously treated with alkylating agents) were treated with a combination of cisplatin and etoposide (VP16-213). Tumor response (i.e., complete response and partial response) was seen in 16 of the 35 patients (i.e., 46%), with 5 complete responses. The response rate in previously untreated patients was 54%, but only 27% in previously treated patients. The median survival was 42 weeks. The toxicity of this regimen was severe. Twelve patients became severely myelosuppressed, including one septic death while severely neutropenic. Treatment with cisplatin and etoposide produces only average tumor response rates and patient survival, but is associated with severe toxicity. There is no evidence of synergy between cisplatin and VP16 in this study.

Adult↗

PubMed1988

Acute renal failure due to focal necrotizing glomerulonephritis in a patient with non-Hodgkin's lymphoma. Resolution with treatment of lymphoma.

Renal disease in association with lymphoma is more prevalent than generally recognized. Glomerulonephritis may occur as a paraneoplastic phenomenon. We report a patient who presented with acute renal failure due to focal necrotizing glomerulonephritis in association with non-Hodgkin's lymphoma in whom the acute renal failure and glomerulonephritis resolved on clinical, biochemical and histological grounds with treatment of the lymphoma. Focal necrotizing glomerulonephritis is extremely uncommon in association with lymphoma and, to our knowledge, this association with follow-up and histological resolution of glomerulonephritis has not previously been reported.

Acute Kidney Injury↗

PubMed1988

A prospective study of cisplatin-based combination chemotherapy in advanced germ cell malignancy: role of maintenance and long-term follow-up.

Two hundred fifty-three patients with advanced germ cell malignancy received initial chemotherapy with cisplatin, vinblastine, and bleomycin followed by surgical resection of residual masses if possible. Patients achieving complete remission (CR) were prospectively randomized to receive 6 months maintenance therapy with vinblastine or no further treatment. CR was achieved in 183 patients (72%) and a further eight patients (4%) had complete resection of residual viable malignancy (no evidence of disease [NED]). Pretreatment factors having a significant adverse influence on response by univariate analysis included extragonadal origin of the tumor, poor performance status, advanced lung or lung and abdominal disease, and elevated serum levels of human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) greater than 1,000 ng/mL. Multivariate regression analysis indicated the independent prognostic factors of significance were advanced lung or advanced lung and abdominal disease, total tumor diameter greater than 10 cm, and a serum level of HCG greater than 1,000 ng/mL. Of the toxicities encountered, myelosuppression was significant, being exacerbated by radiotherapy, and seven deaths occurred from septicemia. Bleomycin pulmonary toxicity occurred in 46% of patients and was severe in 4%, resulting in eight deaths. With a median follow-up of 64 months, relapses have occurred in 25 patients with no significant difference between those patients receiving or not receiving maintenance vinblastine. Eight of these relapses occurred beyond 1 year and four beyond 2 years of follow-up. Presently, 68% of the total patient population is alive and disease-free, with 84% of the CR and NED patients alive and 81% alive and disease-free. It is concluded that with prolonged follow-up, vinblastine maintenance therapy does not improve treatment outcome. Moreover, late relapses occur, cautioning against premature pronouncements of cure.

Adolescent↗

PubMed1987

Randomised study of ticarcillin, cefamandole with or without tobramycin in febrile, neutropenic patients with solid tumors.

A prospective randomised study was conducted comparing the efficacy and toxicity of the antibiotics ticarcillin and cefamandole (TC) with or without tobramycin (TCT) in 100 febrile neutropenic patients with solid tumours undergoing conventional chemotherapy. In this study, neutropenia less than 100/microliter was noted in 31% of 106 evaluable infectious episodes and neutrophil counts less than 1,000/microliter persisted for a median 4 days. Infection was microbiologically documented in 42% of episodes (bacteremia 24%) with gram-negative organisms responsible for 63% of bacterial isolates. Overall, 65% of episodes responded to TC and 76% to TCT (p greater than 0.05). Patients with initial shock bacteremia, pulmonary infection, or gram-negative sepsis responded relatively poorly. Neutrophil nadir and pathogen susceptibility did not influence outcome. Antibiotic toxicity was minimal with no tobramycin-related nephrotoxicity. These results are broadly comparable to those observed with leukemic patients, but the relatively short duration of neutropenia in the solid-tumour patients appears to minimize the need for additional antibiotics provided there is adequate antimicrobial coverage with the initial choice of antibiotics.

Adult↗

PubMed1987

Metastatic adenocarcinoma of unknown primary site. A randomized study of two combination chemotherapy regimens.

Of 101 patients with symptomatic adenocarcinoma or undifferentiated carcinoma of unknown primary site, 95 were evaluable for the effects of two randomized chemotherapy regimens. Forty-eight patients received combination doxorubicin and mitomycin C (DM) and 47 received combination cisplatin, vinblastine and bleomycin (PB). Response rates were not significantly different between the two treatment groups, 42% for DM and 32% for PVB, with an overall response rate of 37.1%. Survival differences for DM and PVB treated groups were not significantly different, with 18 weeks and 25 weeks median survivals respectively. Toxicities were unequal for the two treatment groups with increased haematological toxicity for DM and greater gastrointestinal toxicity for PVB. The authors conclude both therapies were of limited efficacy in the treatment of ACUP patients and emphasize that only symptomatic patients should be considered for such therapies.

Adenocarcinoma↗

PubMed1987

A prospective randomized trial of single-agent versus combination chemotherapy in meningeal carcinomatosis.

Forty-four patients with documented meningeal carcinomatosis (small-cell lung carcinoma [SCLC], 29%; breast carcinoma, 25%) were treated in a prospective randomized trial with intrathecal methotrexate (MTX) 15 mg or MTX plus cytosine arabinoside (Ara-C) 50 mg/m2. Most patients received intrathecal hydrocortisone (HC) each treatment to minimize arachnoiditis. Overall response was 55%. Seven patients achieved complete response. Response to MTX was superior to combined MTX/Ara-C, but not significantly so (61% v 45%; P greater than .10). Response was more frequent if drugs were administered via Ommaya reservoir than by lumbar puncture (65% v 48%; P greater than .10). Concurrent radiotherapy to the CNS was associated with significantly better response (73% v 35%; P less than .05). Small-cell lung carcinoma patients showed the best response (69%). Overall median survival for the whole group was 8 weeks, but responders fared better than nonresponders (median survival, 18 v 7 weeks; P less than .05). Nausea and vomiting were the most common toxicities encountered (45%), but rarely proved limiting. An unusual, previously undocumented reaction to intrathecal HC was noted. MTX is moderately effective in nonleukemic meningeal carcinomatosis, but the addition of Ara-C does not appear to improve results. Pretreatment factors did not predict outcome in this trial.

Adult↗

PubMed1987

Chemotherapy of adult soft tissue sarcoma with combination of doxorubicin and methotrexate.

Thirty-six adult patients with measurable advanced soft tissue sarcoma were treated with a combination of doxorubicin (70 mg/m2) and methotrexate (50 mg/m2) iv every 21 days. Partial remission was seen in ten of 33 evaluable patients (30%). Median duration of remission was 23 weeks, and median survival was 42 weeks. Bone marrow toxicity was the main toxic effect; 23% of the patients had a nadir leukocyte count less than 2.0 X 10(9)/L during therapy. These results do not suggest any therapeutic advantage in adding methotrexate to doxorubicin in this context.

Adult↗

PubMed1986

Analysis of a prospectively randomized comparison of doxorubicin versus 5-fluorouracil, doxorubicin, and BCNU in advanced gastric cancer: implications for future studies.

A multi-institutional cooperative study of patients with locally advanced, recurrent, or metastatic gastric adenocarcinoma who had not previously received chemotherapy was conducted, prospectively randomizing patients to receive either doxorubicin or the three-drug combination, 5-fluorouracil (5-FU), doxorubicin (Adriamycin; Adria Laboratories, Columbus, Ohio), and BCNU (FAB). The 187 evaluable patients were initially stratified according to the presence of measurable or evaluable disease and performance status. There was a significantly higher response rate observed for FAB (40%) compared with doxorubicin (13%) among the 145 measurable-disease patients. Duration of response and survival were significantly longer for FAB in the measurable-disease group, but for the total patient population an early advantage for FAB in time to disease progression and survival was lost with continued follow-up. Median survival was 33 weeks for patients receiving FAB and 19 weeks for those receiving doxorubicin. Significant pretreatment factors adversely affecting survival included poor performance status, weight loss of greater than 10%, and more than two sites of metastases. Toxicity was not severe in either treatment arm, and only thrombocytopenia occurred significantly more often with FAB. It is contended that in the treatment of advanced gastric cancer, chemotherapy only exerts a relatively short-term and modest beneficial effect, most apparent in patients with intermediate tumor bulk. 5-FU remains the most active single agent, and combination chemotherapy has not yet proven its overall worth. Further studies are indicated comparing the most active combinations with 5-FU using optimal doses and schedules, and consideration must be given to the incorporation of no-treatment controls.

Adenocarcinoma↗

PubMed1986

Serum galactosyltransferase as a prognostic marker in patients with solid tumors.

The serum level of galactosyltransferase was measured in a group of 218 patients with a variety of solid tumors and most with advanced disease. The pretreatment enzyme level showed little potential as a diagnostic tumor marker, and its change with treatment did not reflect the initial response. There was, however, a significant correlation between the length of survival and the pretreatment enzyme level. Patients with normal levels survived over twice as long as those with elevated levels. When Cox's proportional hazards regression analysis was used to compare the prognostic potential of galactosyltransferase with a number of known clinical indicators of prognosis, the variable most related to survival was performance status (P less than 10(-4) followed by galactosyltransferase (P = 0.01) and then the extent of disease (P = 0.03). The other variables, such as previous therapy, the type, site, and size of primary tumor, did not contribute significantly to the relationship with survival. The pretreatment level of galactosyltransferase is therefore a relatively independent prognosticator of survival and, as such, could be potentially useful in patient management by increasing the accuracy of the initial assessment of prognosis.

Galactosyltransferases↗

PubMed1985

cis-Diamminedichloroplatinum-induced hypomagnesemia and renal magnesium wasting.

Hypomagnesemia is a well-recognised complication of cis-diamminedichloroplatinum (DDP) treatment. We prospectively evaluated 50 patients with advanced malignant disease receiving DDP for the development of hypomagnesemia. Urinary magnesium excretion was measured in 24 patients. The mean serum magnesium fell from 0.79 mmol/l (normal 0.7-1.1 mmol/l) prior to therapy to 0.55 mmol/l 3 months after commencing DDP. All 50 patients had become hypomagnesemic by this time and 10% were symptomatic, requiring oral magnesium supplementation. At 6 weeks after commencing DDP only four patients had restricted urinary magnesium excretion to less than 1.0 mmol/day. The other patients clearly had inappropriately high levels of urinary magnesium excretion, suggesting that DDP may induce a renal tubular defect in magnesium conservation. Hypomagnesemia is a common complication of DDP therapy which in many patients is asymptomatic. Further, more detailed studies of renal magnesium handling are necessary to determine fully the effect of DDP on urinary magnesium excretion.

Adult↗

PubMed1985

Cisplatin, vinblastine, and bleomycin in inoperable non-small cell lung cancer.

Forty two patients with inoperable non-small cell lung cancer were entered into a phase II study of the combination chemotherapy regimen PVB (cisplatin 60 mg/m2 by intravenous infusion over two hours on day 1, vinblastine 4 mg/m2 by intravenous bolus on days 1 and 2, and bleomycin 15 mg intramuscularly on days 1, 8, and 15), repeated at three weekly intervals. Twelve of 40 evaluable patients (30%) achieved partial responses; there were no complete responses. The median duration of response was 16 weeks (range greater than 8-73 weeks). The median survival of responding patients calculated from entry to the study until death (40 weeks) was superior to that of patients failing to respond (15 weeks). Treatment was accompanied by signs of moderate toxicity, particularly myelosuppression, nausea and vomiting, alopecia, and neuropathy. One patient died from a neutropenic infection. PVB is a moderately toxic regimen for non-small cell lung cancer and appears similar in efficacy and toxicity to high dose cisplatin and vindesine.

Adenocarcinoma↗

PubMed1985

Randomized trial of combination chemotherapy in hormone-resistant metastatic prostate carcinoma.

A prospective randomized study was conducted in 51 patients with stage D hormone-resistant prostatic carcinoma, comparing a combination of doxorubicin and lomustine (DC) with cyclophosphamide and 5-FU (CF). Patients were assessed objectively (employing National Prostate Cancer Project criteria) and subjectively (using a numerical scoring scheme). Each regimen was well tolerated with acceptable levels of myelosuppression. The objective partial response rate was 57% for DC and 8% for CF. Objective stabilization occurred, respectively, in 14% and 44% of the patients. Similarly, DC demonstrated a significantly superior subjective response rate (partial plus complete) of 82%, compared to 48% for CF. Patients with poor initial performance status or liver involvement had significantly lower response rates and reduced survival. Overall, there was no significant difference in survival between the two arms, reflecting the similarity between DC and CF in total objective response rate (partial response plus stable disease). DC provided superior palliation and was well tolerated by an essentially geriatric population.

Aged↗

PubMed1984

Dying of cancer. Factors influencing the place of death of patients.

An analysis of factors influencing the place of death of patients seen by two medical oncology units is reported. There were 1295 recorded deaths of patients from the Royal Prince Alfred Hospital, Sydney, and 688 from The Royal North Shore Hospital of Sydney during 1979-1981; the places of death were known in 1724 instances (87%). Of these, 73% of patients died in hospital, 9% died in terminal nursing care (TNC) institutions, and the remainder at home. Factors influencing the place of death were the place of residence, age, home circumstances-social support, diagnosis, and interval from first contact with the medical oncology unit. Our data indicate that a complex interrelation of these factors determines the place of death. Improvements in community services may allow more patients with cancer to die at home or in TNC institutions, but a substantial proportion of these will still die in major hospitals. Therefore, there is a need for the improvement of palliative care services in these institutions.

Adult↗

PubMed1984

Bleomycin pulmonary toxicity: its relationship to renal dysfunction.

Two hundred seventy-five patients who had received bleomycin were examined for evidence of pulmonary toxicity. Twenty-six patients were diagnosed as having bleomycin pulmonary toxicity and, of these, 20 (77%) were documented as having renal dysfunction without other features recognized to be associated with the development of pulmonary toxicity. In this study renal dysfunction was a most important factor in the development of bleomycin pulmonary toxicity. As bleomycin is often administered with nephrotoxic drugs, it is suggested that renal function should be checked prior to each administration of bleomycin. It is proposed that appropriate dose modifications could significantly reduce the morbidity and mortality associated with bleomycin administration.

Adult↗

PubMed1984

Serum galactosyltransferase isoenzymes as markers for solid tumours in humans.

High resolution agarose isoelectric focusing was used to compare the galactosyltransferase isoenzyme patterns of serum from 9 healthy controls with those from 38 patients with either breast, lung, ovarian, stomach or colonic cancer. At least 12 peaks of enzyme activity were found in every sample, the healthy controls having major forms with isoelectric points of 4.74, 4.87, 4.96, 5.16 and 5.23. Thirty patients (79%) had elevated levels of at least one isoenzyme and 23 (61%) had at least 3 isoenzymes elevated compared to only 10 (26%) patients who had elevated total serum galactosyltransferase activity. The isoenzymes which were most often elevated in the cancer patient group had isoelectric points of 4.93, 5.16 and 4.61. One isoenzyme with an isoelectric point of 4.43 was preferentially elevated in patients with ovarian cancer. Those isoenzymes containing little or no sialic acid were rarely elevated in cancer patients. Although no cancer-associated isoenzyme was detected the quantitative differences observed in the cancer patient group were striking.

Female↗