Biomedical subjects
D W Newling
Publications and source records attributed to D W Newling.
What is 'progression' in prostate cancer?
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The use of adriamycin and its derivatives in the treatment of prostatic cancer.
Adriamycin and the other anthracyclines are amongst the most effective cytotoxic agents at the clinician's disposal. At least one of the reasons for their efficacy is the large number of mechanisms by which they can induce potentially lethal damage in a dividing malignant cell. Adriamycin and epirubicin are amongst the more effective agents in advanced hormone-independent prostate cancer. When given in full doses, they produce a reasonable number of objective as well as subjective responses, but the resultant toxicity precludes their use at high dose in many patients. In a number of well-documented studies, lower doses of these agents have yielded useful subjective responses with minimal toxicity.
Progression delay of prostate tumor skeletal metastasis effects by bisphosphonates.
Prostate tumor cell metastasis to the axial skeleton was induced in male Copenhagen rats using the intravenous injection of syngeneic metastatic R3327-MATLyLu tumor cells and concomitant caval vein clamping. The proliferation of tumor cells in the lumbar region was monitored by the progression, within 19 days post tumor cell injection, of hindleg paralysis which appeared in these animals. Histology confirmed the presence of tumor cells within the lumbar spine in 100% of cases displaying hindleg paralysis. Treatment with either of the bisphosphonate drugs, Cl2MDP or APD, suppressed and delayed the development of hind leg paralysis. Bisphosphonate treatment may be expected to delay the onset of axial skeletal metastasis effects in prostate cancer patients.
Prognostic factors in hormone-resistant progressing cancer of the prostate.
In 224 consecutive patients with hormone-resistant prostatic cancer referred to 2 European Cancer Centres for palliation of painful bone metastases the one year survival for all patients was 24% (2-year survival: 7%). The median survival was 8 months. In univariate analyses the following prognostic factors were identified: performance status, serum creatinine, alkaline phosphatase, duration of response to primary hormone treatment, degree of bone scan involvement and hemoglobin. Multivariate analyses confirmed the four first parameters to be independent factors. A prognostic model was established (no or one risk factors vs 2 risk factors vs 3 or 4 risk factors) based on performance status, creatinine, alkaline phosphatase and hormone response duration. The median survival of these groups was 10 months, 6 months and 3 months, respectively. This model proved to be discriminative in an external data set of 214 patients with hormone-resistant prostatic cancer entered in two prospective trials. The above differences in outcome between readily and simply defined prognostic groups are greater than the differences one can realistically hope to produce using new treatment strategies. These prognostic factors should be taken into account both in the design and interpretation of clinical studies dealing with the treatment of hormone-resistant progressing prostatic cancer and painful bone metastases.
Prostate-specific antigen and other prognostic factors in patients with hormone-resistant prostatic cancer undergoing experimental treatment.
In 58 patients with progressive hormone-resistant metastatic cancer of the prostate, prostate-specific antigen (PSA) greater than 100 micrograms/l, haemoglobin less than 12.0 g/dl and pronounced fatigue were found to be independent adverse prognostic factors. These risk factors distinguished a subgroup of patients with a median survival of 9 months (none or only 1 risk factor present) from a subgroup with a median survival of 4 months (greater than or equal to 2 risk factors present). The clinician should be reluctant to enter patients from the second group into complicated and resource-demanding clinical studies, particularly if such trials require frequent and inconvenient follow-up examinations.
Update of EORTC clinical trials in prostate cancer. The EORTC Genito-Urinary Group.
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Multi-centre phase II study of low dose intravesical epirubicin in the treatment of superficial bladder cancer. Yorkshire and Scottish Urological Cancer Research Groups.
Forty patients with multiple recurrent superficial bladder tumours received an 8-week course of weekly instillations of 4' epirubicin 30 mg in 50 ml saline. The overall response rate was 58% and side effects were minimal.
Organ conservation in bladder cancer.
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Comparison of the effects of high dose Estramustine phosphate and mitomycin C on the time to progression and length of survival of patients with progressive, advanced endocrine-independent prostatic cancer: an interim analysis of EORTC-GU Group study no. 30865.
Patients with hormone escaped advanced progressive prostate cancer were randomized either to receive either high-dose Estramustine phosphate orally or Mitomycin C by i.v. injection every 6 weeks until signs of progression or death supervened. Patients on both arms progressed rapidly, with a median time to progression of 5 months and a median length of survival of only 10 months. Toxicity was very considerable in both arms.
EORTC protocol 30853: orchidectomy versus zoladex plus flutamide in the management of metastatic carcinoma of the prostate. Interim statistical analysis of the side effects of treatment.
The toxicity and side effects of combination therapy with zoladex and flutamide have not been excessive compared with those due to orchidectomy. Pain due to the flare phenomenon has not been observed with zoladex and flutamide. Treatment modification has been necessary in 12 of the 149 patients receiving the combination therapy, compared with one of 148 patients who had surgical castration. Only one patient had flutamide withdrawn because of diarrhea and only five patients had treatment modification because of liver toxicity.
Prostatic specific antigen and the prediction of prognosis in metastatic prostatic cancer.
Serum prostate-specific antigen (PSA) levels were studied in the EORTC trial of zoladex plus flutamide versus orchidectomy in metastatic prostatic cancer. Forty-four of 60 patients had a decrease of PSA to less than or equal to 10 ng/ml at 3 to 6 months after treatment. The combination of a PSA less than 10 ng/ml after 3 to 6 months treatment and less than 15 spots on the bone scintigram at entry gave the highest probability of not having progressed by 24 months. A rising PSA anticipated bone progression by 6 to 12 months in 13 of 28 patients (46%). The PSA at entry to the trial was related to survival; a discriminant of 300 ng/ml distinguished a poor and better risk group. The lowest level of PSA reached during the first 6 months of treatment was also a univariate survival factor.
The response of advanced prostatic cancer to a new non-steroidal antiandrogen: results of a multicenter open phase II study of Casodex. European/Australian Co-operative Group.
Casodex is a non-steroidal antiandrogen which shows marked peripheral selectivity in animals. As an antiandrogen, it has been shown in a dose ranging and an open phase II study to have fewer side-effects than traditional non-steroidal antiandrogens and to be very well tolerated. In the open phase II study, the 50 mg dose was used in 127 evaluable patients who have been treated for up to 1 year. Overall response (i.e. partial response [PR]) was 50% with a further 33% showing stabilization of disease.
Orchidectomy vs. Zoladex plus flutamide in patients with metastatic prostate cancer. The EORTC GU Group.
Treatment with bilateral orchidectomy was compared with Zoladex, 3.6 mg depot, plus flutamide, 250 mg t.i.d., in a randomized prospective study by the European Organization for Research and Treatment of Cancer (EORTC). Small but statistically significant differences in time to subjective and objective progression of disease were found in favor of Zoladex plus flutamide. However, time from objective progression to death was longer in the orchidectomy group. The clinical significance of these differences requires further follow-up and analysis. No difference was found in overall survival between the 2 treatment groups.
A multi-centre phase two study of intravesical epirubicin in the treatment of superficial bladder tumour.
Epirubicin (4'-epi-adriamycin) was used in the treatment of widespread superficial carcinoma of the bladder. Thirty-seven patients received 50 mg in 50 ml of saline retained for 60 min. There was an overall response rate of 59% but this was of short duration. Thirty percent of patients progressed despite therapy. Therapy was associated with an incidence of side effects which necessitated therapy withdrawal in 12 (32.4%) patients. It is concluded that epirubicin, in the dose used in this study, cannot be recommended for routine intravesical chemotherapy and that further studies, at a reduced dosage, are necessary to evaluate this agent.
Ultrasonic detection of a retroperitoneal haematoma causing duodenal obstruction following ureterolithotomy.
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The evolution of active chemotherapy in metastatic and locally advanced bladder cancer.
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History and physical examination in prostate cancer. Which information is essential in diagnosis and follow-up?
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