strontium-radioisotopes and Adenocarcinoma

Metabolic radiotherapy is a new therapy for management of bone pain in patients with bone metastatic prostate carcinoma. Strontium-89 and Samarium-153 concentrate in bone metastases and radiate them. A pain decrease is obtained in 60-70% of cases. Side effects are a significant hematological depression without great clinical consequences if good therapeutic indications are respected. Our multidisciplinary experience of these radionuclides in 54 performed treatments shows a rate of good responders of 66% with a rate of excellent results (total decrease of pain) in 47%. The therapeutic effectiveness is correlated with pain intensity measured by Visual Analogic Scale (VAS) and equivalent dose of morphine. Radionuclide therapy should be applied to patients as early as possible after establishment of bone metastases.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Analgesics, Opioid; Bone Neoplasms; Clinical Trials as Topic; Double-Blind Method; Forecasting; France; Hematologic Diseases; Humans; Male; Middle Aged; Organometallic Compounds; Organophosphorus Compounds; Pain; Palliative Care; Phosphorus Radioisotopes; Prospective Studies; Prostatic Neoplasms; Radioisotopes; Radiopharmaceuticals; Rhenium; Samarium; Strontium; Strontium Radioisotopes; Treatment Outcome

Radiation therapy for locally advanced PCa continues to evolve. A current treatment recommendation for nonmetastatic, high-risk disease includes AS combined with RT. The precise duration and sequencing of AS has not been established but most frequently includes treatment in the neoadjuvant, concomitant and, occasionally, adjuvant periods. As technology allows higher doses without significant increases in morbidity and as clinical data provide proof of a radiation dose response, RT doses continue to escalate. The goal of therapy for metastatic disease continues to focus on the relief of pain and the improvement in quality of life. Multiple studies document the significant role RT plays in achieving these goals. Focal RT and systemic radioisotopes have become the mainstay of management in this patient group and the development of newer isotopes that cause less marrow toxicity will improve the therapeutic ratio and provide an opportunity for their use with systemic chemotherapy. As molecular and genomic technologies advance, directed targeting of critical cellular radiation-response pathways hold the promise of improved radiation response and individualized, tailored therapy.

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Brachytherapy; Chemotherapy, Adjuvant; Clinical Trials, Phase III as Topic; Combined Modality Therapy; Disease-Free Survival; Dose Fractionation, Radiation; Gene Deletion; Gonadotropin-Releasing Hormone; Hemibody Irradiation; Hormone Antagonists; Humans; Male; Neoplasm Metastasis; Neoplasm Proteins; Neoplasm Recurrence, Local; Neutrons; Palliative Care; Prostate-Specific Antigen; Prostatic Neoplasms; Proton Therapy; Radiation Tolerance; Radioisotope Teletherapy; Radiotherapy Dosage; Radiotherapy, Conformal; Randomized Controlled Trials as Topic; Samarium; Strontium Radioisotopes; Survival Rate; Treatment Outcome; Tumor Cells, Cultured

Strontium-89 is a pure Beta-emitting radioactive analogue of calcium that has been shown to be beneficial in the palliation of pain due to osseous metastases from adenocarcinoma of the prostate. The most significant reported toxicity is dose-related, reversible, myelosuppression characterized primarily by thrombocytopenia.. A report of two patients in whom acute myelogenous leukemia (AML) developed after treatment with strontium-89 and a review of the literature are presented.. The two patients described in the current study developed AML 17 months and 26 months, respectively, after exposure to strontium-89 for the treatment of prostate carcinoma. To the authors' knowledge these patients represent the first two reported cases of AML after strontium-89 therapy for prostate carcinoma.. The results of the current study suggest the leukemogenic potential of strontium-89 treatment in humans. To the authors' knowledge, the current study represents the first report of AML after therapeutic exposure to strontium-89. As this agent is used more frequently (and earlier in the disease course) in patients with prostate carcinoma, an increased incidence of secondary AML complicating the clinical management of patients with prostate carcinoma may be observed. [See editorial on pages 497-9, this issue.]

Topics: Adenocarcinoma; Aged; Beta Particles; Bone Neoplasms; Dose-Response Relationship, Radiation; Fatal Outcome; Follow-Up Studies; Humans; Leukemia, Myeloid, Acute; Leukemia, Radiation-Induced; Male; Neoplasms, Second Primary; Palliative Care; Prostatic Neoplasms; Radiopharmaceuticals; Strontium Radioisotopes; Thrombocytopenia

Reports published in the English literature of clinical trials utilizing intravenous strontium 89 (89Sr) in the treatment of patients with prostatic adenocarcinoma metastatic to bone were reviewed. Correlation coefficients were calculated for increasing dose of 89Sr and complete pain relief and complete and partial pain relief. Statistically significant positive correlations were obtained for complete relief of pain. Positive correlations were also found between those patients who had at least partial pain relief (defined as at least a 50% reduction in analgesia requirement), but these did not reach significance. This analysis suggests that a dose response relationship may exist between the dosage of 89Sr administered, and complete relief of pain due to skeletal metastases. The optimal dosage of 89Sr in this clinical situation has not been established, and prospective, carefully executed and analyzed randomized trials will be required to test whether and to what extent dose intensity of 89Sr determines outcome independently of other factors.

Topics: Adenocarcinoma; Bone Neoplasms; Clinical Trials as Topic; Dose-Response Relationship, Drug; Humans; Infusions, Intravenous; Male; Pain; Palliative Care; Prostatic Neoplasms; Research Design; Strontium Radioisotopes

Bone-targeted therapy that combines strontium-89 (Sr-89) with alternating weekly chemohormonal therapy may improve clinical outcomes in patients with metastatic hormone-refractory prostate cancer. This phase II study investigated the addition of Sr-89 to an alternating weekly regimen of doxorubicin and ketoconazole with paclitaxel and estramustine in patients with progressive prostate cancer and bone involvement.. Twenty-nine patients with progressive adenocarcinoma of the prostate and osteoblastic bone metastases who failed conventional hormonal therapy were registered for the study. Of those, 27 were treated with Sr-89 on day 1 of week 1. On weeks 1, 3, and 5, patients received doxorubicin (20 mg/m on day 1) and oral ketoconazole (400 mg 3 times a day for 7 days). On weeks 2, 4, and 6, patients received paclitaxel (100 mg/m(2)) and oral estramustine (280 mg 3 times a day for 7 days). No treatment was given during weeks 7 and 8. Cycles were repeated every 8 weeks.. A > or =50% reduction in prostate-specific antigen level was maintained for at least 8 weeks in 77.7% of the patients (21 patients) at 16 weeks and in 66.6% (18 patients) at 32 weeks. The median progression-free survival was 11.27 months (range, 1.83-29.53), and the median overall survival was 22.67 months (1.83-57.73+). Two patients died during study because of disease progression. Overall, the chemotherapy combined with Sr-89 was well tolerated.. Our results demonstrate that the combination of alternating weekly chemohormonal therapies with Sr-89 demonstrates a prolonged progression-free and overall survival with acceptable toxicity. Further investigation of combination therapies with Sr-89 is warranted.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Combined Modality Therapy; Doxorubicin; Estramustine; Humans; Ketoconazole; Male; Middle Aged; Paclitaxel; Prostate-Specific Antigen; Prostatic Neoplasms; Strontium Radioisotopes; Survival Rate; Treatment Outcome

The clinical management of skeletal metastatic disease is problematic because of the difficulty in treating and accurately monitoring therapy impact and disease progression. This investigation measured serum procollagen type I C-terminal peptide (PICP) concentrations as a semi-quantitative index of bone turnover in patients with metastatic prostatic adenocarcinoma before and following palliative 89Sr chloride therapy. 10 patients with early stage (stage A2, B1 and B2) biopsy-confirmed prostatic adenocarcinoma were investigated (n = 10). Two groups of 10 patients each (n = 10 per group) with advanced (stage D) metastatic prostatic adenocarcinoma who had previously undergone hormonal manipulation were also investigated. One group of patients with scintigraphically documented metastatic bone disease received additional irradiation for new symptomatic bone metastases, whereas the other group received 89Sr chloride therapy. A radioimmunoassay for PICP was used to measure serum concentrations of patients in each of these groups as well as positive and negative controls. The concentration of serum PICP rose from 649 +/- 279 before treatment with external beam radiotherapy to 927 +/- 157 ng ml-1 4 months after therapy (p < 0.05). However, the results demonstrated a four-fold decrease (p < 0.001) in serum PICP in clinical responders to 89Sr chloride therapy versus baseline 4 months after the completion of treatment. The clinical non-responders demonstrated no significant change in PICP concentrations during that interval. This may be due to an increase in untreated bony metastases in the non-89Sr treated group. Although a relatively small representative group of patients was studied, these data demonstrate that serum PICP concentration correlates with clinical response to 89Sr chloride therapy. This objective laboratory technique may be useful for monitoring and predicting the need for 89Sr chloride therapy and optimizing palliative care. It may also be extremely useful in predicting a therapeutic response to such intervention.

Topics: Adenocarcinoma; Aged; Analgesics, Opioid; Biomarkers, Tumor; Bone Neoplasms; Drug Administration Schedule; Humans; Male; Middle Aged; Morphine; Palliative Care; Peptide Fragments; Procollagen; Prostatic Neoplasms; Strontium Radioisotopes; Treatment Outcome

A 67-year old man was diagnosed with advanced prostate cancer with multiple pelvic lymph nodes and multiple bone metastases (cT2N1M1b), with an initial prostate specific antigen of 1,300 ng/ml. Prostate biopsy specimens revealed poorly differentiated adenocarcinoma, Gleason's score 5＋3. He was treated with maximal androgen blockade (MAB) from 2001, but showed resistance to hormone therapy and docetaxel in 2007. External radiation therapy for bone pain was difficult due to multiple lesions. 89Sr therapy was started in 2009. The therapy could be performed 5 times without any side effects. Good pain control and decreasing PSA was obtained at each dose.

Topics: Adenocarcinoma; Aged; Docetaxel; Drug Resistance, Neoplasm; Humans; Male; Orchiectomy; Prostatic Neoplasms; Strontium Radioisotopes; Taxoids

To investigate the therapeutic effects of strontium-89 against osseous metastases of lung cancer.. A total of 126 patients with osseous metastases of lung cancer received strontium-89 treatment ((89)SrCl(2)) at the dose of 148 MBq given through a single intravenous injection. The analgesic effect was evaluated by the changes in the degree, frequency and scores of the pain, and the therapeutic effect assessed by observing the changes in the number and volume of osseous lesions after therapy and compared between different pathological types of lung cancer by Ka-square test.. Within 6 months after the injection, the total pain relief rate was 70.6% (89/126), including 25 (19.8%) cases with pain vanished, suggesting significant alleviation of the pain intensity by the treatment (u=5.361, P<0.01). The frequency of pain was reduced in 78.6% (99/126) of the cases (u=4.589, P<0.01), and the average score of pain decreased significantly from 7.54+/-3.29 to 4.19+/-4.38 (t=6.865, P<0.001). The number and size of lesions decreased by more than 25% in 57 cases, showing a total efficacy rate of 45.2% (57/126). No significant difference was noted in the therapeutic effects among the 4 pathological types of lung cancer (P>0.05).. Strontium-89 is effective for pain relief and tumor focus confinement in osseous metastases of lung cancer. No significant difference has been found in its effect between 4 different pathological types of lung cancer.

Topics: Adenocarcinoma; Adult; Aged; Bone Neoplasms; Carcinoma, Squamous Cell; Female; Humans; Lung Neoplasms; Male; Middle Aged; Pain, Intractable; Strontium Radioisotopes

Topics: Adenocarcinoma; Aged; Humans; Leukemia, Myeloid; Male; Neoplasms, Radiation-Induced; Prostatic Neoplasms; Strontium Radioisotopes

Palliative systemic radionuclide therapy with 89Sr-chloride is a useful intervention for patients with bone pain from metastatic prostatic cancer. Although this radionuclide is highly effective, its mechanism of action remains unresolved. This investigation sought to determine whether systemic radionuclide therapy decreases the production of cell adhesion molecules (E-selectins) that participate in the metastatic process.. Sera were collected from 25 men with metastatic (stage IV) prostate carcinoma who received 89Sr-chloride palliative therapy and from 10 age-matched healthy volunteers. The serum concentration of E-selectin was quantified by an enzyme-linked immunosorbent assay. Sera from 5 patients who received 2 courses of radionuclide therapy were also included in the analysis.. A 2.8-fold decrease in serum E-selectin concentration occurred within 2 mo of radionuclide therapy (P < 0.0001). At 10 mo, however, the concentration increased to a mean (+/- SD) of 151.2 +/- 51.3 ng/mL, surpassing the baseline concentration. This pattern coincided with symptomatic improvement and subsequent health status deterioration. For patients who received 2 courses of radionuclide therapy, a second fall in serum E-selectin concentration followed the second radionuclide treatment.. A significant decrease in serum E-selectin concentration was observed after systemic radionuclide therapy. This finding suggests that expression of cell adhesion molecules, an important determinant of metastatic progression, may be inhibited by 89Sr-chloride.

Topics: Adenocarcinoma; Aged; Bone Neoplasms; E-Selectin; Enzyme-Linked Immunosorbent Assay; Humans; Male; Pain; Pain Management; Pain Measurement; Palliative Care; Prostate-Specific Antigen; Prostatic Neoplasms; Strontium; Strontium Radioisotopes

Topics: Adenocarcinoma; Brachytherapy; Humans; Leukemia, Myeloid, Acute; Male; Neoplasms, Radiation-Induced; Neoplasms, Second Primary; Palliative Care; Prostatic Neoplasms; Risk Factors; Strontium Radioisotopes; Time Factors

Strontium-89 is effective in the palliation of bone pain caused by skeletal metastases. Its primary side effect is mild thrombocytopenia that typically recovers in 3 or 4 months. Subclinical disseminated intravascular coagulation is reported to be present in approximately 10% to 20% of patients with advanced prostate cancer. These patients may be at increased risk for severe marrow depression after radionuclide therapy for bone pain palliation. This report describes a patient with painful bony metastases resulting from prostate carcinoma. He had a normal platelet count and no clinical evidence of a coagulation disorder at the time of strontium-89 therapy, and a severe disseminated intravascular coagulation developed and lead to death after treatment. A normal platelet count before strontium-89 therapy does not preclude subsequent disseminated intravascular coagulation, and we support the Society of Nuclear Medicine's bone pain treatment procedure guideline that patients referred for bone palliation should be screened for disseminated intravascular coagulation before therapy.

Topics: Adenocarcinoma; Aged; Bone Neoplasms; Disseminated Intravascular Coagulation; Humans; Male; Pain, Intractable; Palliative Care; Prostatic Neoplasms; Strontium Radioisotopes

The systemic administration of 89Sr has proven effective in the palliation of painful osseous metastases. Biodistribution studies with the gamma-emitter 85Sr suggest that both its uptake and retention are increased in bone metastases, where increased mineral turnover takes place. To study the pattern and nature of this process further, bones containing metastatic deposits were obtained from three patients who had previously been treated with 148 MBq of 89Sr. The bones were cut into 0.5-1.0 cm sections. The cut surfaces which faced together were marked with India ink, and adjacent sections were submitted for histology and autoradiography. Strontium deposition and retention were observed in regions which exhibited significant osteoblastic activity, mostly in areas adjacent to metastatic deposits, but also in subchondral and endosteal locations, as well as in an area corresponding to a pathological fracture with callus formation. With these exceptions, strontium deposition was not observed in histologically normal bone or within the marrow. Our findings demonstrate directly the selective nature of accumulation and retention of 89Sr and confirm previous clinical impressions.

Topics: Adenocarcinoma; Biopsy; Bone Neoplasms; Breast Neoplasms; Female; Humans; Male; Pain; Palliative Care; Prostatic Neoplasms; Strontium Radioisotopes; Tissue Distribution

A patient with metastatic prostate cancer was found to have low-grade disseminated intravascular coagulation (DIC). He had significant bone pain despite external-beam radiotherapy and was given 89Sr with subsequent thrombocytopenia and epistaxis. The patient died from generalized hemorrhage 36 days postinjection. Although it is not possible to establish a causal relationship between the 89Sr and DIC, practitioners should be alert to complications associated with the primary disorder which might occur at a time to raise concern about the intervention.

Topics: Adenocarcinoma; Aged; Bone Neoplasms; Disseminated Intravascular Coagulation; Epistaxis; Fatal Outcome; Humans; Male; Prostatic Neoplasms; Strontium Radioisotopes; Thrombocytopenia

Strontium-89 has been used for the treatment of painful bony metastases in patients suffering from disseminated adenocarcinoma of the prostate, with a variable proportion of patients obtaining clinically significant reductions in analgesic requirements. Based on data revealing enhancement of continuous low-dose rate irradiation by low-dose cisplatin in murine models, a protocol using 148 MBq (4 mCi) of 89Sr and 35 mg/m2 of cisplatin infused over 2 days, 1 and 4 wk after administration of the radioisotope was undertaken. Preliminary data suggest good pain relief with 55% of 18 patients entered thus far obtaining at least a 50% reduction in analgesic requirements. Improvements in total alkaline phosphatase and serum lactate dehydrogenase have consistently been seen, with some patients exhibiting improvements in hemoglobin, tumor markers and bone scans. Toxicity appears to be mild, with no life-threatening complications. In particular, myelosuppression after one course of treatment was modest, but retreatments in two patients has resulted in grade 3 hematologic toxicity. Two patients developed a "pain flare" after administration of cisplatin. Further accrual to this study will allow more accurate determination of pain response rate, and improved evaluation of parameters of objective response.

Topics: Adenocarcinoma; Aged; Bone Neoplasms; Cisplatin; Combined Modality Therapy; Drug Evaluation; Humans; Male; Middle Aged; Pain; Prostatic Neoplasms; Strontium Radioisotopes

We present dosimetry for spinal metastases and red bone marrow in two patients who received 89Sr therapy for disseminated prostatic carcinoma. Absorbed dose to metastases was estimated by combining 85Sr gamma camera studies with computed tomographic measurements of bone mass, and doses of 20 cGy/MBq and 24 cGy/MBq were found for vertebral metastases that uniformly involved the bodies of L3 and D12 respectively. Absorbed dose to red bone marrow was estimated from total body strontium retention studies using the ICRP model for bone dosimetry, and a ratio of metastatic to marrow dose of around 10 was found in each patient. Although they received comparable treatment activities of around 200 MBq, the patients showed markedly different haematological response, this difference being confirmed when each received a second 89Sr treatment 6 months after the first. As a result, clinically significant thrombocytopenia occurred in one patient which prevented further radiostrontium therapy being given.

Topics: Adenocarcinoma; Aged; Bone Marrow Diseases; Brachytherapy; Energy Transfer; Follow-Up Studies; Hematologic Diseases; Humans; Male; Prostatic Neoplasms; Radiotherapy Dosage; Spinal Neoplasms; Strontium Radioisotopes; Tomography, X-Ray Computed; Whole-Body Counting

The osteotropic radionuclides 89Sr and 32P are now mainly used in the treatment of bone metastases. This therapy is palliative and is mainly directed at alleviating pain. The indications, procedure, treatment result and side effects are described as discussed. Bone metastases of iodinophilous thyroid carcinomas represent a special case. These can be treated selectively with 131I. However, complete regression of the tumour by means of radioactive iodine is only rarely achieved in bone metastases. Nevertheless, the complaints and symptoms are definitely alleviated even with relatively small radiation doses, similar to the therapy employing strontium.

Topics: Adenocarcinoma; Bone Neoplasms; Female; Humans; Iodine Radioisotopes; Male; Prostatic Neoplasms; Rectal Neoplasms; Strontium Radioisotopes; Thyroid Neoplasms

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

Topics: Adenocarcinoma; Adult; Aged; Arthritis; Bone Diseases; Bone Neoplasms; Breast Neoplasms; Colonic Neoplasms; Female; Fluorine; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Neoplasm Metastasis; Osteitis Deformans; Prostatic Neoplasms; Radiation Dosage; Radiation Monitoring; Radiography; Radioisotopes; Radionuclide Imaging; Ribs; Shoulder; Skull Neoplasms; Strontium Radioisotopes; Technetium; Thoracic Neoplasms

Topics: Adenocarcinoma; Carcinoma, Bronchogenic; Gallium; Humans; Liver Neoplasms; Male; Mediastinal Neoplasms; Middle Aged; Radioisotopes; Radionuclide Imaging; Strontium Radioisotopes

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