melphalan and chromic-phosphate

Intraperitoneal radioactive chromic phosphate was administered to 69 patients with Stage I and II ovarian carcinoma who had undergone comprehensive surgical staging. Intestinal obstruction requiring surgical intervention occurred in four patients and was the most severe complication. Abdominal pain was the most common post-therapy complaint. Attention to time and technique of drug administration could minimize complications.

Topics: Adolescent; Adult; Aged; Chromium; Chromium Compounds; Female; Follow-Up Studies; Humans; Injections, Intraperitoneal; Melphalan; Middle Aged; Ovarian Neoplasms; Phosphates; Phosphorus Radioisotopes; Prospective Studies; Radiotherapy

Ovarian cancer is the leading cause of death from gynecological malignancies and the fourth most frequent fatal malignancy in women. Despite improved surgical techniques as many as 20% of women with early stage disease will eventually relapse and die from their disease. The post-operative management of these women remains controversial. Here we present the long term follow-up data of our previously published study, as well as the incidence of second primary malignancies in these women.. Two hundred fifty-seven eligible patients with stage I, IIA 'high risk' ovarian carcinoma and IIB, IIIO (disease confined to pelvis) were randomized to either whole abdominal radiotherapy 2.250 rads in ten fractions (107 patients), melphalan 8 mg/m2/d x 4 weeks x 18 courses (106 patients) or intraperitoneal chromic phosphate 10-20 mCi (44 patients). All patients were initially treated with pelvic radiotherapy.. Overall survival estimates at 10 years were: 45% in the whole abdominal radiotherapy arm; 49% in the melphalan arm and 50% in the intraperitoneal chromic phosphate arm (P = 0.30). Relapse-free survival estimates at 10 years were: 50% in the whole abdominal radiotherapy arm, 62% in the melphalan arm and 51% in the chromic phosphate arm (P = 0.147). Long term follow-up has not demonstrated a significant difference between treatment arms. Second primary malignancies developed in 29 women (11%) after 2,229 person years of follow-up. This compares to 18.7 second primary malignancies which would have been expected in this group of age-matched controls and was statistically significant (P = 0.018). There was no significant difference in the total number of second primary malignancies between treatment arms. Melphalan appeared to be associated with an increased risk of developing leukemia/myelodysplastic syndrome compared to the whole abdominal radiotherapy arm (P = 0.06).. Long-term follow-up has not demonstrated a significant difference in overall or disease free survival between treatment arms. An excess of second primary malignancies (35%) was observed suggesting that lifelong surveillance is required in this population. Further research with newer treatment programs are needed to improve the cure rates in this population.

Topics: Antineoplastic Agents, Alkylating; Brachytherapy; Canada; Chromium Compounds; Combined Modality Therapy; Disease-Free Survival; Dose Fractionation, Radiation; Female; Humans; Melphalan; Neoplasm Staging; Neoplasms, Second Primary; Ovarian Neoplasms; Phosphates; Survival Rate; Time Factors

Intraperitoneal radioactive chromic phosphate was administered to 69 patients with Stage I and II ovarian carcinoma who had undergone comprehensive surgical staging. Intestinal obstruction requiring surgical intervention occurred in four patients and was the most severe complication. Abdominal pain was the most common post-therapy complaint. Attention to time and technique of drug administration could minimize complications.

Topics: Adolescent; Adult; Aged; Chromium; Chromium Compounds; Female; Follow-Up Studies; Humans; Injections, Intraperitoneal; Melphalan; Middle Aged; Ovarian Neoplasms; Phosphates; Phosphorus Radioisotopes; Prospective Studies; Radiotherapy

Two hundred fifty-seven eligible patients with stage I, IIA "high risk" ovarian carcinoma and IIB, IIIO (disease confined to pelvis), were randomized to either total abdominal radiotherapy (arm A) 2,250 rad in 20 fractions (107 patients), melphalan (arm B) 8 mg/m2/d X 4 every 4 weeks X 18 courses (106 patients), or intraperitoneal chromic phosphate (arm C) 10 to 20 mCi (44 patients). All patients were initially treated with pelvic radiotherapy; arm A, 2,250 rad in ten fractions; and arms B and C, 4,500 rad in 20 fractions. Entry to arm C was discontinued early because of toxicity. In a multifactor analysis using proportional hazards models, no significant difference in survival was observed although there was a marginally significant difference in disease-free survival (P = .015) with arm B being superior to arm A. Stage (P less than .0001), grade (P less than .0001), and histology (P less than .008) were predictors of survival in the multifactor analysis. Performance status, age, and residual disease were significant predictors in the single factor analysis but were not predictive when correction was made for the effects of stage, grade, and histology. Five-year survival rates are 62% for arm A, 61% for arm B, and 66% for arm C. Median duration of follow-up is 8 years. Long-term complications of radiotherapy were seen in 19 patients on arm A, 11 on arm B, and 11 on arm C. Four patients who had received melphalan developed either a myelodysplastic syndrome or acute leukemia. Violations in covering the whole abdominal target volume were correlated with survival.

Topics: Chromium; Chromium Compounds; Clinical Trials as Topic; Combined Modality Therapy; Female; Humans; Melphalan; Ovarian Neoplasms; Phosphates; Phosphorus Radioisotopes; Prognosis; Random Allocation

As part of a randomized trial evaluating several treatment programs in the management of poor prognosis, early stage ovarian cancer, 53 patients were randomized to receive a combination of pelvic external beam radiation, 4000 rad plus 10-20 millicuries of radioactive chromic phosphate given intraperitoneally. Only 35 patients (66%) actually received the chromic phosphate. The other 18 did not enter this phase of treatment for a variety of reasons documented in this report. Ten (29%) of the 35 patients receiving the full course of treatment had significant long term side effects with the median time to onset of symptom being 9 months after the chronic phosphate was given. There were no treatment-related deaths. The complications could not be related to the dose of the isotope, the technique of administration, nor any other definable predisposing factors. This combination is not recommended for further study.

Topics: Brachytherapy; Chromium; Chromium Compounds; Female; Humans; Melphalan; Ovarian Neoplasms; Phosphates; Phosphorus Radioisotopes