strontium-radioisotopes and Carcinoma

Painful bone metastases are most frequent in patients with advanced prostate or breast carcinoma. The aim of this study was to compare the analgesic effect of radionuclide therapy using Sr and Sm-EDTMP in patients with painful bone metastases of these tumours.. One hundred patients treated with radionuclide bone palliation therapy were analysed. The study population consisted of 60 male patients with advanced prostate carcinoma and 40 female patients with advanced breast carcinoma. Fifty patients (30 men and 20 women) were treated with Sr (150 MBq). The other 50 patients were treated with Sm-EDTMP (37 MBq x kg). The treatment efficacy was evaluated by a visual analogue scale (VAS), Karnofsky performance scale, and dosage of analgesic drugs used.. Complete pain relief was found in 40% of women and 40% of men treated using Sm-EDTMP and in 25% of women and 33% of men treated with Sr. No analgesic effect occurred in 20% of patients. A better analgesic effect was found in cases of osteoblastic metastases compared to mixed metastases. Statistically significant reduction of pain intensity, use of analgesic drugs and improvement of performance in Karnofsky scale was found in cases of both radionuclides.. The analgesic effects of Sr and Sm-EDTMP was similar in both prostate and breast carcinoma. However, the effect was dependent on the type of metastases; better response was observed in cases of osteoblastic metastases than in patients with mixed metastases. Severe adverse reactions after this therapy were rare.

Topics: Aged; Bone Neoplasms; Breast Neoplasms; Carcinoma; Female; Humans; Male; Middle Aged; Organometallic Compounds; Organophosphorus Compounds; Pain; Pain Measurement; Palliative Care; Prostatic Neoplasms; Radiopharmaceuticals; Strontium Radioisotopes; Treatment Outcome

The objectives of the current study were to determine the maximum tolerated dose and to evaluate the efficacy of gemcitabine given in combination with strontium-89 to patients with androgen independent prostate carcinoma.. Patients with androgen-independent prostate carcinoma and painful osteoblastic bone metastases were eligible. On a 12-week course, patients received gemcitabine (600 mg/m(2) or 800 mg/m(2)) on Days 1, 8, 15, 43, 50, and 57. A single dose of strontium-89 (55 microCi/kg) was administered on Day 8.. Fifteen patients were registered, and all were assessable for response and toxicity. Four patients were treated at Dose Level 1 (gemcitabine 600 mg/m(2)) without dose-limiting toxicity. Eleven patients received a total of 13 courses at Dose Level 2 (gemcitabine 800 mg/m(2)). Platelet nadirs of 25000-50000 platelets per microL were common at Dose Level 2, and 1 patient had Grade 4 thrombocytopenia that was dose-limiting. Granulocyte nadirs up to < 500 granulocytes per microL occurred in 4 patients at Dose Level 2 and were reversible. There were no responses, as measured by prostate specific antigen concentration, although 6 patients (40%) had stable disease.. The authors concluded that 800 mg/m(2) gemcitabine was the maximum tolerated dose for the combination. The study was terminated on the basis that an overall response rate > than 10% was unlikely. Further study at this dose level and schedule is not warranted. .

Topics: Aged; Bone Neoplasms; Carcinoma; Combined Modality Therapy; Deoxycytidine; Drug Administration Schedule; Gemcitabine; Humans; Injections, Intravenous; Male; Maximum Tolerated Dose; Middle Aged; Neoplasms, Hormone-Dependent; Prostate-Specific Antigen; Prostatic Neoplasms; Radiation-Sensitizing Agents; Strontium; Strontium Radioisotopes; Testosterone

Estramustine phosphate (EMP) and vinblastine have radiosensitizing properties and significant activity against hormone refractory prostate carcinoma. Strontium-89 is a palliative agent that acts as a selective radiation source for bone metastasis. The combination of EMP, vinblastine, and strontium-89 was developed to exploit the potential for radiosynergy. PATIENTS AND METHODS Forty-four patients at the Brown Oncology Group affiliated hospitals were treated with oral EMP 600 mg/m2 daily on Weeks 1-4 and 7-10, vinblastine 4 mg/m2 intravenously once each week on Weeks 1-4 and 7-10, and strontium-89 2.2 MBq/kg on Day 1. Courses were repeated every 12 weeks. Response assessment was based on a change in the serum prostate specific antigen (PSA) levels, correlated with change in measurable disease and bone scan appearance.. A greater than or equal to 50% decline in PSA for at least 6 weeks was observed in 21 patients (48%, 95% confidence interval, 33-62%). Median duration of response was 23 weeks (range, 6-70.8 weeks). The median survival was 13 months with 1- and 2-year survival rates of 55% and 25%, respectively. After completion of protocol therapy, a retrospective review showed that only nine patients received subsequent palliative external beam radiation after progression.. The addition of strontium-89 to the regimen of EMP and vinblastine can be delivered safely and in repeated doses, provides effective palliation, and may decrease the need for future radiation therapy. A randomized trial is necessary to quantify these effects.

Topics: Administration, Oral; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Carcinoma; Combined Modality Therapy; Estramustine; Humans; Infusions, Intravenous; Male; Middle Aged; Palliative Care; Prostate-Specific Antigen; Prostatic Neoplasms; Strontium Radioisotopes; Treatment Outcome; Vinblastine

Prostate carcinoma is linked to osteoblastic metastasis. We therefore investigated the value of bone-targeted consolidation therapy in selected patients with advanced androgen-independent carcinoma of the prostate.. 103 patients received induction chemotherapy, consisting of ketoconazole and doxorubicin alternating with estramustine and vinblastine. After two or three cycles of induction chemotherapy, we randomly assigned 72 patients who were clinically stable or responders to receive doxorubicin with or without strontium-89 (Sr-89) every week for 6 weeks.. Overall 62 of the 103 (60%, 95% CI 50-70) patients had a 50% or greater reduction in serum prostate-specific antigen concentration that was maintained for at least 8 weeks, and 43 (42%, 32-52) had an 80% or greater reduction. 49 (52%) patients with bone pain at registration had complete resolution of pain. After follow-up of 67 patients until death, the estimated median survival for all 103 patients was 17.5 months (range 0.5-37.7). For the 36 patients randomly assigned to receive Sr-89 and doxorubicin, the median survival time was 27.7 months (4.9-37.7), and for the 36 who received doxorubicin alone it was 16.8 months (4.4-34.2) (p=0.0014). The hazard ratio was 2.76 (95% CI 1.44-5.29).. Bone-targeted consolidation therapy consisting of one dose of Sr-89 plus doxorubicin once a week for 6 weeks, when given to patients with stable or responding advanced androgen-independent carcinoma of the prostate after induction chemotherapy, improved overall survival.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Bone Neoplasms; Carcinoma; Doxorubicin; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Strontium Radioisotopes; Survival Analysis; Texas

Many radiopharmaceuticals used for medical diagnosis and therapy are beta emitters; however, the mechanism of the cell death caused by beta-irradiation is not well understood. The objective of this study was to investigate the apoptosis of human breast carcinoma MCF-7 cell lines induced by Strontium-89 (⁸⁹Sr) and its regulation and control mechanism. High-metastatic Breast Carcinoma MCF-7 cells were cultured in vitro using ⁸⁹Sr with different radioactive concentration. The inhibition rate of cell proliferation was measured by MTT color matching method. The cell cycle retardation, apoptosis conditions, mitochondrion transmembrane potential difference and Fas expression were tested and analyzed. The genes P53 and bcl-2 expressions was also analyzed using immunity histochemical analysis. After being induced by ⁸⁹Sr with various of radioactive concentration, it was found that the inhibition of cell proliferation of MCF-7 cells was obviously, the retardation of cell cycle occurred mainly in G2-M. It was also found that the obvious apoptosis occurred after being induced by ⁸⁹Sr, the highest apoptosis rate reached 46.28%. The expressions of Fas acceptor and P53 gene increased, while bcl-2 gene expression decreasesd. These findings demonstrate that in the ranges of a certain radioactive concentration, the inhibition rate of MCF-7 cell proliferation and retardation of cell cycle had positive correlation with the concentration of ⁸⁹Sr. And the mitochondrion transmembrane potential decrease would induce the apoptosis of MCF-7 cell notably, which were controlled by P53 and bcl-2 genes, involved with the Fas acceptor.

Topics: Apoptosis; Breast Neoplasms; Carcinoma; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Radiation; fas Receptor; Female; Gene Expression Profiling; Humans; Membrane Potentials; Mitochondria; Proto-Oncogene Proteins c-bcl-2; Radiopharmaceuticals; Strontium Radioisotopes; Tumor Suppressor Protein p53

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Humans; Leukemia, Myeloid, Acute; Leukemia, Radiation-Induced; Male; Neoadjuvant Therapy; Neoplasms, Second Primary; Prostatic Neoplasms; Radiopharmaceuticals; Risk Factors; Strontium Radioisotopes

Until now, patients with a progressive prostatic cancer, in whom all therapies failed and the disease spread locally and distally, was considered "a lost patient"; because it did not exist an effective therapy easily to be used. The skeletal pain control is a serious problem and it is a great responsibility also for the Urologists especially if the patient has not a short survival time and the quality of life is very poor. Physicians feel the need for a systemic, well tolerated and effective therapy also for a long time, uniform and repeatable, able to be efficient for these patients. Strontium 89 chloride seems to offer all these possibilities and to be the best procedure for Urologist, Radiotherapists and Nuclear Specialists in order to satisfy the patients requirements. International research has shown Sr-849 Chloride is a powerful new therapy. Sr-89 Chloride is a radiopharmaceutical product for the treatment of painful metastases from prostatic cancer. It is a new treatment but its effectiveness is well documented and results are reported in the most important international literature. In our Department a clinical research has started and our purpose is to produce more data for a clinical and biological evaluation of the results, hoping that a similar research will extend as a multicenter study.

Topics: Bone Neoplasms; Carcinoma; Humans; Male; Pain; Prostatic Neoplasms; Radiation Protection; Radiotherapy Dosage; Remission Induction; Strontium; Strontium Radioisotopes

We have shown previously that the risk of tumor initiation, promotion, and progression in animals initiated with alkylating agents can be drastically altered by hyperthermia treatments. We show here that ionizing radiation can also alter the risk of tumor initiation by alkylating agents. Using a two-step skin tumorigenesis protocol in female SENCAR mice (initiation by MNNG, promotion with TPA), we exposed the dorsal skin of the mice to various doses of 90Sr/90Y beta radiation near the time of initiation. The radiation produced a dose-dependent reduction in the number of papillomas which appeared after TPA promotion, with about a 20% reduction in animals receiving 0.5 Gy surface dose just before initiation, about 50% reduction after 2.5 Gy, and greater than 80% at doses above 5 Gy. A dose of 2.5 Gy in animals initiated with DMBA produced no significant reduction. One skin hyperthermia treatment (44 degrees C, 30 min) along with radiation in MNNG-initiated animals partially blocked the protective effect of radiation and increased the papilloma frequency. Radiation (2.5 Gy) given either 6 days before or after MNNG initiation was less effective but still reduced papilloma frequency about 20%. In sharp contrast to the marked reduction in papilloma formation, these same animals showed no change in carcinoma frequency with any of the doses or schedules of beta radiation. MNNG initiation alone produced three types of initiated cells. One type, produced in low yield, was promotion-independent with a high probability of progression to a carcinoma and appeared unaffected by the radiation. A second type, produced in intermediate yield, was promotion-dependent and also had a high progression probability, but was likewise unaffected by the radiation. The third and most abundant type was promotion-dependent with a very low progression probability. Radiation exposure resulted in a decrease in the risk of an MNNG initiation event which led only to the third type of cell. The data therefore indicate that the risk of some, but not all, tumor-initiating events caused by alkylating agents can be reduced by an exposure to ionizing radiation.

Topics: Animals; Beta Particles; Carcinoma; Female; Methylnitronitrosoguanidine; Mice; Papilloma; Skin Neoplasms; Strontium Radioisotopes

Ten patients with disseminated bone metastases, nine from prostatic and one from renal cell carcinoma, were treated with intravenous strontium-89. Half the patients experienced significant improvement in pain control and increased general well-being for an average of 14 weeks. Sequential radiophosphate bone scanning showed decreased activity in lesions present at the time of therapy, with subsequent remineralization of the metastases on radiographs. Some patients showed simultaneous reduction in alkaline and acid phosphatase levels. These objective findings prove a physiologic basis for the clinical improvement. Treatments, however, did not prevent progression at initially uninvolved sites, particularly in the extremities.

Topics: Aged; Aged, 80 and over; Bone Neoplasms; Carcinoma; Follow-Up Studies; Humans; Male; Middle Aged; Prostatic Neoplasms; Radiography; Radionuclide Imaging; Strontium Radioisotopes

In the urological department of the Wilhelminenspital altogether 22 patients with incurable bone pains in metastasizing carcinoma were treated with radioisotopes between 1976 and 1980. 32P and 89Sr were used in a dosage of 3 times 3 mCi and once 1 mCi. A reaction to the therapy could be proved in 46%, in 23% the success could be estimated as very good. Clinic and therapy were discussed with the help of own cases and literature.

Topics: Adenocarcinoma; Aged; Bone Neoplasms; Carcinoma; Female; Humans; Kidney Neoplasms; Male; Neoplasm Staging; Palliative Care; Phosphorus Radioisotopes; Prostatic Neoplasms; Strontium Radioisotopes

Data now available on the risks of radiation-induced fatal cancer and hereditary disease and radionuclide metabolism suggest that limits on the rates of intake of 90Sr, 226Ra and 239Pu at work, presently recommended by the International Commission on Radiological Protection, might be in need of considerable revision one with another and with the limit for uniform exposure of the whole body.

Topics: Body Burden; Breast Neoplasms; Carcinoma; Dose-Response Relationship, Radiation; Female; Genetic Diseases, Inborn; Humans; Leukemia; Lung Neoplasms; Male; Maximum Allowable Concentration; Neoplasms, Radiation-Induced; Nuclear Warfare; Occupational Medicine; Osteosarcoma; Paranasal Sinus Neoplasms; Plutonium; Radiation Injuries; Radiation Tolerance; Radium; Strontium Radioisotopes; Thyroid Neoplasms

A total of 146 patients were investigated for the presence of osseous metastases with 99mTc polyphosphate or 99mTc pyrophosphate bone scans. Results of bone imaging were retrospectively compared to roentgenographic results surveying similar anatomic areas in 128 patients. This comparison revealed that roentgenographic interpretations were in error in 19% of the cases. Thirty-three patients had bone scans and roentgenograms that were in agreement and considered abnormal, but in more than one third of these cases the patients had multiple abnormalities that were shown by the bone scan but were not recognized roentgenographically. In consideration of the low toxicity, ready availability, economy, shortened procedure time, and low radiation dose associated with the use of these new bone-seeking agents, it is concluded that they are superior to roentgenograms and previously utilized radionuclides for early detection of osseous metastases.

Topics: Bone Neoplasms; Carcinoma; Diphosphates; Fluorine; Humans; Lung Neoplasms; Male; Neoplasm Metastasis; Phosphates; Prostatic Neoplasms; Radioisotopes; Radionuclide Imaging; Scintillation Counting; Strontium Radioisotopes; Urinary Bladder Neoplasms

Topics: Adenocarcinoma; Bone Neoplasms; Breast Neoplasms; Carcinoma; Female; Humans; Male; Neoplasm Metastasis; Phosphates; Prostatic Neoplasms; Radionuclide Imaging; Strontium Radioisotopes; Technetium

Topics: Age Factors; Aged; Carcinoma; Conjunctiva; Cornea; Entropion; Eye Neoplasms; Humans; Male; Strontium Radioisotopes

Topics: Animals; Bronchi; Carcinoma; Carcinoma, Squamous Cell; Epithelium; Lung Neoplasms; Radiation Injuries; Radiation Injuries, Experimental; Rats; Strontium; Strontium Radioisotopes