Fractionated radioimmunotherapy with 90Y-clivatuzumab tetraxetan and low-dose gemcitabine is active in advanced pancreatic cancer: A phase 1 trial

It has been demonstrated that the humanized clivatuzumab tetraxetan (hPAM4) antibody targets pancreatic ductal carcinoma selectively. After a trial of radioimmunotherapy that determined the maximum tolerated dose of single-dose yttrium-90-labeled hPAM4 (90Y-hPAM4) and produced objective responses in patients with advanced pancreatic ductal carcinoma, the authors studied fractionated radioimmunotherapy combined with low-dose gemcitabine in this disease

Current status of systemic intravenous radiopharmaceuticals for the treatment of painful metastatic bone disease

Purpose : Intractable bone pain secondary to bone metastasis from prostate, lung, breast, and other malignancies is a major problem in the management of the oncological patient. Because a number of factors are implicated in the pathophysiology of bone pain, a multidisciplinary approach in its assessment and treatment is often required. Treatment often includes the use of analgesic drug therapy; however, radiation therapy, hormonal therapy, chemotherapy, and surgery may also be needed. Methods and Materials : The use of systemic radionuclide therapy may often be helpful to relieve bone pain and improve the quality of life. In the setting of diffuse bone metastasis, intractable to conventional therapy, various radioisotopes have been advocated. These include phosphorous-32, iodine-131, strontium-89, yttrium-90, samarium-153, and rhenium-186, often as either the anionic phosphate or as a ligand (HEDP, EDTMP). Results : When these agents are used, pain relief often occurs in approximately 2–4 weeks and lasts several weeks to months with responses seen in 60–80% of patients, depending on the extent of disease and stage the patient is treated. Retreatment has been possible in certain cases with further palliation being offered and improvement in the various quality of life parameters being noted. Conclusion : Myelotoxicity has been a limiting factor with certain isotopes and has led to the development of less toxic bone seeking agents. Although these each have unique physical and biokinetic properties requiring different doses and protocols for administration, they all appear to localize in osteoblastic metastatic sites in sufficient amounts to provide bone pain palliation

Systemic metabolic radiopharmaceutical therapy in the treatment of metastatic bone pain

Bone pain due to skeletal metastases constitutes the most common type of chronic pain among patients with cancer. It significantly decreases the patient's quality of life and is associated with comorbidities, such as hypercalcemia, pathologic fractures and spinal cord compression. Approximately 65% of patients with prostate or breast cancer and 35% of those with advanced lung, thyroid, and kidney cancers will have symptomatic skeletal metastases. The management of bone pain is extremely difficult and involves a multidisciplinary approach, which usually includes analgesics, hormone therapies, bisphosphonates, external beam radiation, and systemic radiopharmaceuticals. In patients with extensive osseous metastases, systemic radiopharmaceuticals should be the preferred adjunctive therapy for pain palliation. In this article, we review the current approved radiopharmaceutical armamentarium for bone pain palliation, focusing on indications, patient selection, efficacy, and different biochemical characteristics and toxicity of strontium-89 chloride, samarium-153 lexidronam, and rhenium-186 etidronate. A brief discussion on the available data on rhenium-188 is presented focusing on its major advantages and disadvantages. We also perform a concise appraisal of the other available treatment options, including pharmacologic and hormonal treatment modalities, external beam radiation, and bisphosphonates. Finally, the available data on combination therapy of radiopharmaceuticals with bisphosphonates or chemotherapy are discussed

Proposal on the use of Xenon-133 against COVID-19

Since we are able to bring ionizing radiation in the form of a gas cloud to the respiratory system, we have wondered whether Xenon-133 inhalation could be exploited as a treatment option against Covid-19 respiratory virus infections, and urge colleagues in the scientific research community who have the capability to do so to explore the merits of using Xenon-133 in this way to determine whether its usefulness against the Covid-19 virus is indeed genuine. •Perfusion of the respiratory system with ionizing radiation.•Auger electrons hypothesized impact on the Covid-19 virus.•Free radicals impacting the Covid-19 virus in the respiratory space

Radiopharmaceuticals: When and how to use them to treat metastatic bone pain. J Support Oncol 2011;9:197

one pain due to osseous metastasis constitutes the most frequent type of pain in cancer patients. It is significantly related to poor quality of life in the final stages of the disease. Although it is most commonly seen in the advanced stages, patients can often present with bone pain as the first symptom of cancer, particularly in prostate and breast cancers. The prevalence of painful osseous metastases varies among the different types of cancers. Approximately 65% of patients with prostate or breast cancer and 35% of those with advanced cancers of the lung, thyroid, and kidney will have symptomatic skeletal metastases. Breast and prostate cancers are responsible for more than 80% of cases of symptomatic bone metastases in any oncologic practice. 1,2 This type of pain is distinct from neuropathic, visceral, or other types of somatic pain, such as inflammatory and arthritic pain, and presents with certain features during its course: initially, it is dull and of low intensity and progresses to a chronic state with intermittent severe breakthrough episodes of acute pain. Generally, the bone pain exacerbates at the end of dose of the analgesic, and it is often difficult to treat without being accompanied by significant, unwanted side effects. The pathophysiology is not well understood, and multiple mechanisms are postulated. 3 Tumor-induced cytokines, stimulating factors released by tumor cells, and direct nerve injury have all been proposed as mechanisms that mediate skeletal pain. Infiltration of bone trabeculae and matrix by tumor-causing osteolysis also generates skeletal pain, which is supported by the inhibitory osteoclastic effect of bisphosphonates in the treatment of bone pain. 5 The appearance of bone involvement may be the first and only sign of solid tumor spread, detected in many instances before the primary site. Due to a high prevalence of osseous metastasis, screening whole-body bone scintigraphy has been part of the initial staging algorithm of prostate and breast cancers. Also, when osseous metastasis is suspected clinically or detected by other imaging modalities, bone scintigraphy helps to delineate the extension and severity of skeletal involvement and classify lesions as predominantly osteoblastic, lytic, or mixed type, which will be crucial in the correct treatment plan, as discussed later in this article. Abstract Bone pain due to skeletal metastases constitutes the most common type of cancer-related pain. The management of bone pain remains challenging and is not standardized. In patients with multifocal osteoblastic metastases, systemic radiopharmaceuticals should be the preferred adjunctive therapy for pain palliation. The lack of general knowledge about radiopharmaceuticals, their clinical utility and safety profiles, constitutes the major cause for their underutilization. Our goal is to review the indications, selection criteria, efficacy, and toxicities of two approved radiopharmaceuticals for bone pain palliation: strontium-89 and samarium-153. Finally, a brief review of the data on combination therapy with bisphosphonates or chemotherapy is included. The appropriate management of painful skeletal metastasis is complicated and expensive and should be carried out by a multidisciplinary approach. Most of the therapies targeted to destroy the tumor itself are effective methods of pain control, like chemotherapeutic agents, external beam radiation (XRT), radiofrequency ablation (RF), and surgery. However, they sometimes can be invasive (ie, surgery and RF) or arduous to administer (ie, chemotherapeutic regiments), can provide incomplete pain control, or can be accompanied by unwanted side effects, particularly in patients with extensive metastatic disease. Medications without tumoricidal effect targeted to diminish the pain associated with metastasis, such as nonsteroidal antiinflammatory drugs (NSAIDs), steroids, and opiates, are equally useful but also have dose-limiting side effects. Despite a large armamentarium of available analgesics, it has been reported that at least 45% of cancer patients have insufficient and undermanaged pain control, due to a poor estimation of the patient's pain by the physician, inadequate pain assessment, treatment-associated side effects, and lack of knowledge of all treatment options. 7 Symptomatic pain assessment must be performed with standardized measurement tools administered at appropriate intervals. Consistent pain measurement and systematic recording of analgesic use across clinical trials would enhance comparability of findings and facilitate the development of evidence-based guidelines for the management of metastatic bone pain. For instance, a consensus on palliative end-point measurements in bone metastases has been in use for XRT trials and can be used as a reference in future trials of other palliative modalities. Among available therapies, systemic radiopharmaceuticals are the least understood and used by clinical oncologists and pain specialists. Our major goal is to increase awareness of available radiopharmaceuticals for bone pain palliation. We will review the current indications, patient selection criteria, efficacy, and toxicity profile of two radiopharmaceuticals which are currently approved for bone pain palliation: strontium-89 chloride (Sr-89) and samarium-153 lexidronam (Sm-153). Finally, the available data on combination therapy of radiopharmaceuticals with bisphosphonates or chemotherapy will be discussed. The use of other available palliative treatment options, including pharmacological, surgical, and hormonal modalities, is beyond the scope of this article. However, since XRT is the main alternate modality to radiopharmaceuticals for the treatment of painful osseous metastasis, a short discussion of this method will be provided below. External Beam Radiation for Pain Control The therapeutic purposes of XRT for bone metastases are pain relief as measured by reduced pain intensity scores, elimination or reduction of analgesic usage, functional improvement such as increased ambulation, and reduction in the risk of fracture in weight-bearing bones. Extensive data from large multicenter, randomized trials conducted by the Radiation Therapy Oncology Group (RTOG) have demonstrated that 80%-90% of patients receiving radiation therapy for osseous metastases will experience complete or partial pain relief, typically within 10 -14 days of the initiation of therapy with minimal side effects. However, XRT has limited use in extensive multifocal osseous metastasis or in metastatic sites included in previously treated radiation fields. Also, it does not preclude the development of other metastatic foci away from or nearby sites that were treated for disease. Although hemibody or total-body radiation can sometimes be utilized, the total delivered dose is limited due to its high risk of inducing severe bone marrow suppression. In addition, patients must be hospitalized and given extensive supportive care. Studies have shown that approximately 80% of patients may be successfully treated with sequential whole-skeleton radiation, in which 6 -7 Gy is administered as a single fraction to either the upper and lower parts of the body, followed by a second dose of 6 -8 Gy, given 4 -6 weeks later, to the remainder of the body. 10 Although the expected response is within 24 -48 hours, depending on the location of the radiation treatment field, 60% of patients experience adverse side effects such as diarrhea, nausea, lymphedema, fatigue, radiation pneumonitis, and hair loss, all of which can be quite challenging. 7,11 Also, the total cost of this treatment is significantly higher than conventional single or fractionated localized XRT. Therefore, patients with widespread metastatic bone disease or osseous lesions within previously treated radiation fields may be ideal candidates for treatment with systemic radiopharmaceuticals. The possibility of combining radiopharmaceuticals and localized XRT is exciting, although limited data are available. 12 Targeted Systemic Radionuclide Therapy with Bone-Seeking Radiopharmaceuticals Systemic radionuclide therapy has shown its value in the management of painful bone metastasis in current clinical practice. Different indications for clinical use of these agents, besides pain palliation, have also been studied in recent clinical trials, which include radioisotope treatment of hemophilic arthropathy