(32)P in the treatment of myeloproliferative disorders.

UNLABELLED: (32)P has been available for the treatment of myeloproliferative neoplasms (MPNs) for over seventy years. It was first used in 1938 by John H Lawrence in the treatment of polycythaemia and chronic leukaemias. With the introduction of agents such as hydroxycarbamide, interferon and anagrelide the role of (32)P has been diminished. Today, Polycythaemia Rubra Vera (PRV) and Essential Thrombocythaemia (ET) remain the only myeloproliferative conditions in which (32)P is indicated. MATERIALS AND METHODS: We carried out a retrospective review of all patients who had received 32P in Northern Ireland over a 24 year period. The time to successful response, duration of response, and associated complications were reviewed. RESULTS: (32)P was successful in inducing remission in 90% of patients. This remission was sustained following one dose without the need for further therapy in 37% of cases. 47% required repeated doses. 26% required recommencement of alternative therapies. No cases of thrombosis, myelofibrosis or acute leukaemia were observed. DISCUSSION: We conclude that (32)P is a well-tolerated and efficacious treatment option in the elderly. We discuss our results compared with previous work in this area. (32)P will continue to be offered to elderly patients in our practice.

Phosphorus-32, a clinically available drug, inhibits cancer growth by inducing DNA double-strand breakage.

Radioisotopes that emit electrons (beta particles), such as radioiodine, can effectively kill target cells, including cancer cells. Aqueous 32P[PO4] is a pure beta-emitter that has been used for several decades to treat non-malignant human myeloproliferative diseases. 32P[PO4] was directly compared to a more powerful pure beta-emitter, the clinically important 90Y isotope. In vitro, 32P[PO4] was more effective at killing cells than was the more powerful isotope 90Y (P ≤ 0.001) and also caused substantially more double-stranded DNA breaks than did 90Y. In vivo, a single low-dose intravenous dose of aqueous elemental 32P significantly inhibited tumor growth in the syngeneic murine cancer model (P ≤ 0.001). This effect is exerted by direct incorporation into nascent DNA chains, resulting in double-stranded breakage, a unique mechanism not duplicatable by other, more powerful electron-emitting radioisotopes. 32P[PO4] should be considered for human clinical trials as a potential novel anti-cancer drug.

[A clinical study on the treatment of mucocele by bleomyin A5 combined with phosphorus-32 colloid].

OBJECTIVE: To evaluate the effect of bleomyin A5 combined with phosphorus-32 colloid in the treatment of mucocele. METHODS: A total of 214 patients divided into three groups, bleomyin A5 (50 cases), phosphorus-32 colloid (50 cases) and bleomyin A5 combined with phosphorus-32 colloid (114 cases). RESULTS: The efficacy of bleomyin A5 group, phosphorus-32 colloid group, and bleomyin A5 combined with phosphorus-32 colloid group was 84% (42/50), 82% (41/50) and 98% (112/114), respectively. There were significant difference in efficacy among the three groups (P < 0.05). The phosphorus-32 colloid group and the bleomyin A5 group had no significant difference in efficacy (P > 0.05). CONCLUSIONS: The independent use of bleomyin A5 and phosphorus-32 colloid is effective, but the combined use of the two methods is more effective.

32P-patch contact brachyradiotherapy in the management of recalcitrant keloids and hypertrophic scars.

Keloids are the result of excessive fibroblast proliferation and then over-abundant collagen deposition. There is no method able to guarantee absolute success in the therapeutic approach to keloids. Our case report involves a female patient with six lesions treated with a 32P-patch brachyradiotherapy. Pre-treatment and adjuvant treatment of the lesions were performed with thiomucase, 5-fluoruracil, procaine and triamcinolone. Taking into account the activity contained in each of the patches and the total radiation dose to be administered according to clinical practice, dosimetric calculations were done for each lesion. Separate silicone patches with chromic [32P]phosphate were designed for each lesion based on these calculations. Total remission was achieved in three treated lesions. The other lesions did not achieve total remission yet, but their sizes are diminishing. The differences observed in treatment outcome may be related with lesion features, adjuvant treatments and/or treatment schedule.

Polycythemia vera: a review.

Polycythemia vera (PV) is a clonal stem cell disorder characterized by increased erythrocyte production. Its etiology is not fully understood, and hemorrhage, thrombosis, and hyperviscosity may occur at any time during the course of this disorder. Treatment depends on the most affected cell type, duration and severity of the condition, and patient age. PV treatment can involve phlebotomy, administration of myelosuppressive agents, and biologic therapy. The inconsonant nature of the disease and complications related to its various treatments present nursing care challenges. Nurses must work with patients with PV to ensure compliance with treatment, teach awareness of disease- and treatment-related complications, and provide needed support.

32P Radiosynoviorthesis in children with hemophilia.

BACKGROUND: This study was performed to prospectively evaluate the safety, efficacy, and cost of injecting P-colloid into joints of children with hemophilia and synovitis to decrease the rate of joint bleeding. PATIENTS AND METHODS: Eligibility included a diagnosis of hemophilia, history of more than six hemorrhages into a joint within a 6-month period, and evidence of synovitis by objective imaging. With written, informed consent, 0.25 to 1.0 mCi of P-colloid was injected into the problem joints. Safety was monitored by external beta-scanning and physical assessment. Efficacy was determined by analysis of the change in joint hemorrhage frequency from 6 months before and up to 96 months after the injection using a signed-rank test. Physical assessment and pain assessment were analyzed similarly using values obtained within 1 week before and 6 months after the radiosynoviorthesis. Cost was modeled using charges from the authors' institution in relation to existing alternative therapies. RESULTS: One hundred injections were given into 91 joints in 59 children. Seven children had high-titer neutralizing antibodies to factor VIII or IX. Nine children were infected with HIV. Joints injected included 44 ankles, 19 knees, 27 elbows, and 1 shoulder. Nine joints required reinjection. All children showed a significant decrease in bleeding rate (P < 0.0001) and pain (P = 0.03), with improved physical function (P = 0.02). In one child acute lymphocytic leukemia developed, but it was judged unrelated to the two P injections that he had received 3 and 10 months before the leukemia diagnosis. There were no cases of bleeding, infection, or inflammation caused by the injection. Cost was substantially less than medical and surgical alternatives. CONCLUSIONS: Radiosynoviorthesis is effective in limiting the frequency of joint hemorrhage, decreasing pain and improving function in children with hemophilia. However, long-term safety studies are needed.

Monte Carlo characterization of a 32P source for intravascular brachytherapy.

In this work, we have calculated the two-dimensional dose distribution in water for a 32P intravascular brachytherapy source wire using the EGSnrc Monte Carlo code. The beta source (Guidant Vascular Intervention) has a radioactive core with a length of 27 mm and a diameter of 0.24 mm. The dose parameters required by the AAPM TG-60 formalism are discussed and calculated. Dose rate evaluated at the reference point is 0.1311+/-0.0001 Gy min(-1) mCi(-1). For the beta source studied, the dose distribution is uniform along the axial direction z for a given radial position p for - 10 mm< or =z< or =10 mm and p< or =7 mm. In such a dose-uniformity region, the dose field can be characterized by one-dimensional dose distribution, D(p), the dose distribution on the transverse axis. Beyond this region a two-dimensional (2D) description is necessary. However, for the long beta source wire the anisotropy function proposed by the TG-60 formalism becomes indefinable when the radial distance exceeds penetration depth of beta electrons. We have proposed that the anisotropy function be expressed in the cylindrical coordinate system, instead of a polar system, to remedy this deficiency. For practical purposes, the entire 2D dose distribution and the dose parameters calculated in the work are tabulated for ease of use.

Plasma erythropoietin concentrations in polycythaemia vera with special reference to myelosuppressive therapy.

In 80 patients with polycythaemia vera (PV) a total of 108 venous blood samples were obtained and analysed for EDTA-plasma erythropoietin (EPO) concentration. At the time of study 21 of the PV patients were newly diagnosed and had prior to blood sampling neither received phlebotomy treatment nor therapy with myelosuppressive agents; these subjects had a mean plasma EPO concentration of 0.5+/-0.9 IU/L. Thirty-seven patients treated with phlebotomy only had a mean plasma EPO concentration of 2.5+/-2.9 IU/L. The mean plasma EPO concentrations for 26 patients treated with hydroxyurea, 13 patients treated with radiophosphorous and 11 patients given a combination of myelosuppressive agents were 8.9+/-8.0, 10.9+/-12.6 and 7.2+/-7.4 IU/L, respectively. Untreated patients and patients on phlebotomy only had significantly lower values for plasma EPO than patients on therapy with myelosuppressive drugs. This finding persisted also after a correction for differences in haemoglobin levels had been introduced. Thereby, the present results would suggest a difference in the EPO feedback system in untreated and phlebotomised PV patients compared to PV patients treated with myelosuppressive agents.

Use of colloids of chromic [32P] phosphate in treatment of solid tumors.

In order to evaluate the effectiveness of an intratumorally single dose of chromic [32P] phosphate for the treatment of solid tumors, studies of bioelimination, biodistribution, and therapeutic action were carried out. Only for comparative purposes were similar studies undertaken using a solution of sodium [32P] orthophosphate-gelatin. Results show that when sodium [32P] orthophosphate-gelatin was intratumorally injected, the percentage of total elimination, after 32 days of treatment, was equal to 85.90 +/- 8.70%, with a higher percentage in urine (64.50 +/- 13.70%) than in feces (21.40 +/- 4.50%). In biodistribution studies, the greater percentage was found in bone (15.54 +/- 2.21%), whereas only 2.51 +/- 0.39% remained in the tumor. When chromic [32P] phosphate was intratumorally injected, we found that the total elimination was equal to 51.70 +/- 6.90%, with a higher amount in feces (32.70 +/- 4.80%) than in urine (19.00 +/- 3.60%). Biodistribution studies demonstrated that 28.93 +/- 1.30% was still in the tumor and 19.01 +/- 1.30% of the injected activity was found in the liver. On the other hand, when therapeutic action was evaluated, no tumoral regression was observed. These results demonstrate that the colloid of chromic [32P] phosphate cannot be used in the treatment of solid tumors as it mobilizes from the injection point, delivering a high dose to the entire organism.

Great particles (32P) chromic phosphate for treatment of solid tumors

With the purpose studying the effectivity of an intratumoral single dose of chromic [(32)P] phosphate with great particles for the treatment of solid tumors, studies of biolimination, biodistribution and therapeutic action were carried out. Only for comparative purpose, similar studies were undertaken using a solution of sodium [(32)P] orthophosphategelatine. The results show that when sodium [(32)P] orthophosphategelatine is used, the percentage of total elimination is (85.90+8,70) per cent with a higler percentage in urine (64.50+13.70) per cent than in faeces (21.40+4.50) per cent. In biodistribution studies, the greater percentage is found in bone (15.54+2.21) per cent while only a (2.51+0.39) per cent remains in the tumor. When great particles chromic [(32)P] phosphate was intratumorally injected, we determined that the total elimination is equal (36.28+6.27) per cent, finding a higler amount in faeces (29.44+5.26) per cent than in urine (6.84+2.21) per cent. Biodistribution studies demonstrated that (49.82+5.41) per cent remains in the tumor and (9.63+4.89) per cent of the injected activity is found in the liver. On the other hand, when therapeutic action was evoluted, we observed that the percentage of tumor regression (P.T.R) is 52.0 per cent for the tumors injected with chromic [(32)P] phosphate and 0.0 per cent for those injected with sodium [(32)P] orthophosphate-gelatine. These results show that the great particles colloid of chromic [(32)P] phosphate is not safe enough for the tratment of solid tumors, since it is mobilezed from the injection point, delivering a high dose to the whole organism.

Great particles (32P) chromic phosphate for treatment of solid tumors

With the purpose studying the effectivity of an intratumoral single dose of chromic [(32)P] phosphate with great particles for the treatment of solid tumors, studies of biolimination, biodistribution and therapeutic action were carried out. Only for comparative purpose, similar studies were undertaken using a solution of sodium [(32)P] orthophosphategelatine. The results show that when sodium [(32)P] orthophosphategelatine is used, the percentage of total elimination is (85.90+8,70) per cent with a higler percentage in urine (64.50+13.70) per cent than in faeces (21.40+4.50) per cent. In biodistribution studies, the greater percentage is found in bone (15.54+2.21) per cent while only a (2.51+0.39) per cent remains in the tumor. When great particles chromic [(32)P] phosphate was intratumorally injected, we determined that the total elimination is equal (36.28+6.27) per cent, finding a higler amount in faeces (29.44+5.26) per cent than in urine (6.84+2.21) per cent. Biodistribution studies demonstrated that (49.82+5.41) per cent remains in the tumor and (9.63+4.89) per cent of the injected activity is found in the liver. On the other hand, when therapeutic action was evoluted, we observed that the percentage of tumor regression (P.T.R) is 52.0 per cent for the tumors injected with chromic [(32)P] phosphate and 0.0 per cent for those injected with sodium [(32)P] orthophosphate-gelatine. These results show that the great particles colloid of chromic [(32)P] phosphate is not safe enough for the tratment of solid tumors, since it is mobilezed from the injection point, delivering a high dose to the whole organism. (AU)

Adjuvant intraperitoneal chromic phosphate therapy in a woman with early ovarian carcinoma and pelvic infection with resulting catastrophic complications.

Women diagnosed with early stage ovarian cancer may be considered for adjuvant therapy. Intraperitoneal chromic phosphate (P-32) is commonly used in these patients with few complications. A woman found to have early stage ovarian cancer was given intraperitoneal P-32 in the presence of a lingering pelvic infection, which is usually not mentioned as a contraindication to its use. Radiation damage to the small bowel and cecum developed as did damage to the ureter and bladder, which then required surgery.

Intraperitoneal P-32 is not an effective consolidation therapy after a negative second-look laparotomy for epithelial carcinoma of the ovary.

Thirty-four patients with epithelial carcinoma of the ovary were entered into a trial of adjuvant intraperitoneal P-32 following induction chemotherapy and a negative second-look laparotomy. The breakdown by initial Stage was Stage IC, 5; Stage II, 3; Stage III optimal, 22; and Stage III suboptimal, 4. Previous treatment consisted of 4-12 cycles (median 6) of cisplatin or carboplatin-based combination chemotherapy. Fifteen millicuries of P-32 were instilled via a Tenckhoff catheter placed at the time of second-look laparotomy. Because of a 22% incidence of bowel injury in the first 23 patients, the P-32 dose was reduced to 12 mCi in the last 11 patients. To date, there have been no bowel injuries at the lower dose. Eighteen of the 34 (53%) patients have relapsed with a median time to relapse of 20 months and a median follow-up for all patients of 31 months. There has been no difference in the relapse rate between a dose of 12 and 15 mCi. Intraperitoneal P-32 does not appear to reduce the relapse rate following a negative second-look laparotomy. The incidence of bowel injury is dose dependent and is higher than that seen in patients treated as an adjuvant following initial surgery without subsequent chemotherapy or second-look laparotomy.

Adjuvant intraperitoneal chromic phosphate therapy for women with apparent early ovarian carcinoma who have not undergone comprehensive surgical staging.

Forty-nine women with apparent Stage I and II ovarian carcinoma received intraperitoneal phosphate 32 as the only adjuvant therapy after primary surgery. In addition to bilateral salpingo-oophorectomy, 40 (82%) had analysis of peritoneal cytology, and 35 (71%) underwent omentectomy. Random peritoneal biopsies and retroperitoneal lymph node sampling were not done in any of these patients. The overall and disease-free survival rates were 86% and 75%, respectively, with no significant differences by stage, histologic grade, histologic type, or low-risk versus high-risk subsets recognized in patients who received comprehensive surgical staging. Seven (58%) of 12 patients had lymph node metastasis as the first site of recurrence, including two of three with late recurrences. Significant morbidity related to intraperitoneal chromic phosphate (32P) occurred in one (2%) woman. These results emphasize the need for comprehensive surgical staging of women with apparent early ovarian carcinoma to aid in the selection of appropriate initial adjuvant therapy.

Adjuvant internal hepatic radiotherapy using colloidal 32P chromic phosphate in colorectal cancer.

The purpose of the study is to investigate the value of adjuvant radiotherapy given in the form of colloidal chromic phosphate 32P suspension administered via portal vein, in preventing the growth of occult metastases in the liver. Twenty two patients (10 patients of treated group with 12 controls) were followed 12 months after operation. There was no significant change in the CBC and liver functions after administration of 32P labeled colloidal chromic phosphate. Although local recurrence rates were very similar in both groups of colorectal cancer (3/12 in the control group and 4/10 in the treated group), liver metastasis rates were quite different: 4/12 in the control group and none (0/10) in the treated group. In conclusion, 32P labeled colloidal chromic phosphate is expected to prevent liver metastases of completely resected colorectal cancer.

Intraperitoneal chromic phosphate in ovarian cancer: risks and benefits.

Between March 1977 and December 1985, 59 patients were treated with intraperitoneal chromic phosphate at The University of Alabama Birmingham Hospitals and its affiliates. Twenty-seven patients received primary adjuvant therapy. Thirty-two patients were treated "secondarily" after tumor recurrence or after a "positive" second-look laparotomy. Associated morbidity was noted to be 12% with reoperation required in 7%. Early stage and grade tumors demonstrate a good prognosis. Little, if any, benefit was demonstrated in "secondary" therapy of advanced stage and grade tumors.

Colloidal chromic phosphate 32P synovectomy in antigen-induced arthritis in the rabbit.

Radioisotopes have been employed in the therapy of chronic arthritis, in particular, rheumatoid arthritis for many years. A variety of isotopes have been popularized, and in the last ten years a colloidal solution of radioactive chromic phosphate 32P has been in use apparently with equivalent efficacy to others such as 169erbium, 90yttrium, and 165dysprosium. No controlled studies on this modality have been reported and few animal studies were found. The efficacy of therapeutic doses of 32P as a medical synovectomy and its effect on rabbit joints with antigen-induced arthritis were observed in 62 arthritic knee joints in 31 adult rabbits treated on one side with 0.1 microCi of 32P, the opposite serving as control. The animals were observed over a period of 11 months and examined by histologic and biochemical means. The synovium showed no evidence of radiation necrosis in treated joints. Cartilage of treated and control joints showed similar changes consistent with chronic arthritis, persistent synovitis, progressive chondrocyte degeneration, and decreased matrix metachromasia. The radiosynovectomy had neither removed synovium nor protected the cartilage. Its efficacy in humans is therefore questionable.

Intraperitoneal radioactive chromic phosphate P 32 in the treatment of ovarian cancer.

The use of intraperitoneal radioisotopes in the management of women with ovarian cancer is controversial. We analyzed the experience with intraperitoneal chromic phosphate P 32 at our institution, from October 1979 to February 1983, in 22 patients with various stages and grades of ovarian malignancy. Survival in stage I is 87.5% and in stage II, 50%. Survival is 88.9% among patients with grade 1 tumors and 33.3% for those with grade 3 lesions. Morbidity related to chromic phosphate P 32 was minimal; small bowel obstruction occurred in only one patient who had also received external pelvic irradiation. Our results suggest that chromic phosphate P 32 is a safe, well tolerated, inexpensive, and effective adjuvant to surgery in the management of selected patients with ovarian malignancy.

Ovarian carcinoma: adjuvant treatment with P-32.

Twenty-eight patients with ovarian carcinoma received 555 MBq of labeled chromic phosphate (P-32) intraperitoneally. Indications for treatment included a high-grade tumor, extracapsular involvement, positive cytologic findings, or residual tumor. Fifteen patients (group 1) had stage I, II, or III completely resected tumor; 13 patients (group 2) had microscopic or less than 3-mm lesions at second-look laparotomy following combination chemotherapy. A major complication occurred in one patient; two patients had minor complications. Overall, 24 of 28 patients (85.7%) were alive at 11-77 months; 23 (82.1%) had no evidence of tumor. Fifteen of 15 (100%) group 1 patients and eight of 13 (61.5%) group 2 patients did not have tumor relapse after 30 months and 28 1/2 months, respectively. P-32 was found to be an effective adjuvant treatment in a select group of patients with ovarian carcinoma who were at high risk for intraabdominal recurrence.

Intraperitoneal chromic phosphate P 32 suspension therapy of malignant peritoneal cytology in endometrial carcinoma.

Malignant peritoneal cytology in patients with endometrial carcinoma is a poor prognostic feature, identifying patients at high risk for early intra-abdominal recurrence. Between 1977 and January, 1983, 65 women with endometrial carcinoma who had malignant peritoneal cytology were treated with adjuvant intraperitoneal radioactive chromic phosphate P 32 suspension. Fifty-three patients (80%) were clinical Stage I, nine (14%) were Stage II, and three (7%) were clinical Stage III. Life-table estimates of disease-free survival were 89% for clinical Stage I patients and 94% for surgical Stage I patients beyond 24 months. One patient developed an intraperitoneal recurrence, four had simultaneous intraperitoneal and extraperitoneal recurrences, and six developed recurrences outside of the peritoneal cavity. Few significant acute complications occurred after therapy with radioactive chromic phosphate P 32 suspension. Chronic intestinal morbidity that required surgical correction was encountered in five of 17 patients (29%) who received adjuvant pelvic radiation, compared to none of the 48 patients (0%) who received only radioactive chromic phosphate P 32 suspension (p less than 0.001). Intraperitoneal instillation of radioactive chromic phosphate P 32 suspension is effective therapy for patients with malignant peritoneal cytology from endometrial carcinoma. Caution should be exercised when radioactive chromic phosphate P 32 suspension and external radiation therapy are combined.