Halperin7e_CH29

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C H A P T E R 2 9  Radioimmunotherapy and Unsealed Radionuclide Therapy

neck, was reported. Intense activity and doses were docu- mented; however, improvements in local control and survival were inconclusive. 105 A randomized trial was performed on 30 patients with unresectable adenocarcinoma of the pancreas. The patients were randomized to 5-FU and EBRT with or without intratumoral 32 P. All patients received adjuvant gem- citabine. There was more liquefaction in the 32 P arm (78% vs. 8%). There was no difference in survival but an increase in serious adverse events in the 32 P arm. 106

30 to 100 mCi are used for ablation, whereas higher activities in the range of 100 to 300 mCi are used for known residual disease, recurrence, or metastatic disease. If possible, patient- specific dosimetry should be used to determine the activity in the metastatic setting. 99 Using this approach, a dose <200 cGy is calculated to the blood (bone marrow) and ≤120 mCi of 131 I being retained after 48 hours. This can result in administered activities between 75 and 659 mCi without the development of leukemia, permanent bone marrow suppression, or pul- monary fibrosis. 100 Diagnostic 131 I scanning and thyroglobulin measurement are required for follow-up. Phosphorus 32 Physical Properties : t ½ = 14.3 days; radiation decay: β (1.71 MeV maximum and 1.69 MeV mean); γ (none). Clinical Utility : Phosphorus 32 ( 32 P) represents one of the earliest agents in this class and perhaps is the most fre- quently studied for a wide variety of indications and routes of administration. In its aqueous form (Na 2 PO 3 ), the agent was employed for the systemic therapy of chronic myeloge- nous leukemia and polycythemia vera. Orthopedic surgeons and rheumatologists have evaluated the agent for intra- articular management of persistent synovial effusions and hemarthroses secondary to hemophilia and leukemias. 101,102 The agent has been placed in indwelling catheters to treat CNS lesions. The colloidal form of the agent (as chromic phosphate) became a standard modality for management of malignant pleural and peritoneal effusions in the 1960s and 1970s, driv- ing numerous clinical investigations. Anecdotal reports sug- gesting significant activity were infrequently corroborated in randomized clinical trials. Following drainage of abdomi- nal ascites or pleural effusions, up to 5 mCi of the agent was instilled and patients were placed in various positions to enhance distribution. The nature of the disease processes and prior therapy often predisposed patients to preinstilla- tion adhesions with bowel or lung immobility, and distribution of the agent proved difficult. This indication has largely been replaced by instillations of various antibiotic or chemothera- peutic compounds. Following identification of a subset of early-stage, high- risk ovarian cancer patients (FIGO stage Ia or Ib [grade 3], or stage 1c or II [any grade], or any stage I/II patient with clear cell histology), the Gynecologic Oncology Group (GOG), North Central Cancer Treatment Group (NCCTG), and Southwest Oncology Group (SWOG) undertook a randomized trial assigning patients to either a single dose of 15 mCi of IP 32 P or cyclophosphamide 1 g/m 2 and cisplatin 100 mg/m 2 every 21 days for three cycles. Prior to instillation of the radioac- tive material through multiperforated indwelling peritoneal dialysis catheters, 99m Tc was instilled to ensure free flow and even distribution of the therapeutic agent. IP 32 P was admin- istered within 10 days but not >6 weeks following laparot- omy. Ten-year follow-up of the study population suggested a modest reduction in intra-abdominal recurrence rate for the chemotherapy population but only a small and nonsignificant improvement in survival. These findings were corroborated by other reports. 103 ( 32 )P localization in bone created interest in the use of the orthophosphate form of the isotope for painful skeletal metastases with 85% of the administered dose ultimately incorporated into bone. However, priming regimens includ- ing androgenic agents prior to isotope administration were prolonged, beneficial results modest, and myelotoxicity sig- nificant; use of the agent for this indication is not ideal 104 and has largely been abandoned. In the 1990s, a series of patients, treated with direct intra- lesional infusions of 32 P colloidal chromic phosphate for unre- sectable tumors of the liver, CNS, pancreas, and head and

Section II

Strontium-89 Chloride (Metastron, GE Healthcare, Chalfont St. Giles, UK) Physical Properties : t ½

= 50.5 days; radiation decay: β (1.463

MeV maximum and 0.583 MeV mean); γ (none). 89 Sr, a calcium analogue, is administered as an IV injection at doses of 4 mCi. Clinical Utility : The Trans-Canada study randomized 126 patients with painful metastatic castrate-resistant prostate cancer to EBRT to painful bone sites with either 89 Sr or pla- cebo. 107 A significant improvement in the following endpoints was noted in the 89 Sr arm: (1) intake of analgesics, (2) progres- sion of pain, and (3) quality of life analysis. Multiple phase II and III trials have subsequently been performed using 89 Sr, showing favorable results. The conclusion of the review was that 89 Sr should be considered for the treatment of metastatic cancer where pain control is an issue and the bone scan shows activity. 108 The TRAPEZE trial is a prospective random- ized trial comparing docetaxel alone or with zoledronic acid (ZA), 89 Sr, or both. Results revealed that 89 Sr combined with docetaxel significantly improved progression-free survival. 109 Samarium-153 Lexidronam (Quadramet, Cytogen, Princeton, NJ) Physical Properties : t ½ = 46.3 hours; radiation decay: β (0.81 MeV maximum and 0.23 MeV mean); γ (maximum energy 103 keV). Clinical Utility : Samarium-153 EDTMP ( 153 Sm) is a bone- seeking agent consisting of radioactive samarium and a telephosphonate chelator, EDTMP. The recommended thera- peutic dose is 1.0 mCi/kg, administered intravenously over a period of 1 minute through a secure indwelling catheter and followed by a saline flush. Extensive preclinical and clinical investigations have demonstrated the safety and effective- ness profile of 153 Sm-EDTMP. 110,111 Although primarily used alone, there is increasing interest in consideration of combi- nation therapy with the bisphosphonates and taxane-based chemotherapeutics. The use of 153 Sm-EDTMP has been evaluated in osseous metastases for primary osteosarcomas. Anderson et al. 112 investigated the use of gemcitabine as a radiosensitizer to increase 153 Sm-EDTMP effectiveness. Using 30 mCi/kg (aver- age of 1,640 mCi), they found acceptable toxicity and objective response in 8 of 14 patients investigated. Treatment of osteo- sarcoma with 153 Sm has been further reviewed; 153Sm used as monotherapy or in combination with chemotherapy, stem cell transplant or EBRT. 153 maximum); γ (270 keV maximum). Clinical Utility : The phase III ALSYMPCA (Alpharadin in Symptomatic Prostate Cancer Patients) trial confirmed the clinical utility of 223 Ra (Xofigo) for the treatment of cas- trate-resistant adenocarcinoma of the prostate. A total of 921 patients who had received, were not eligible to receive, or declined docetaxel were randomized 2:1 to receive six instillations of Xofigo (50 kBq/kg) every 4 weeks or placebo. Radium-223 Chloride Physical Properties : t ½ = 11.4 days; radiation decay: α (6 MeV