Development of anemia and recovery in prostate cancer patients treated with combined androgen blockade and radiotherapy.

BACKGROUND: The objective of this study was to document previously unreported anemia in prostate cancer patients treated with neoadjuvant combined androgen blockade (CAB) and pelvic radiotherapy (XRT). METHODS: Four institutions treated 141 patients (mean age +/- SD, 70.9 +/- 6.5 years) with zoladex 3.6 mg injection subcutaneous depot monthly and flutamide 250 mg orally three times per day for 2 months (CAB), followed by zoladex and flutamide with concurrent XRT (65-70 Gy) for 7-8 weeks. RESULTS: After the XRT, the patients were randomized to receive no further treatment (Z- group, 71 patients) or zoladex alone (Z+ group, 70 patients) for 2 years. Hemoglobin (Hb) levels decreased > or = 1 g/dl (mean +/- SE, 2.1 +/- 0.1 g/dl) in 98/131 patients (75%) after 2 months of CAB, and > or = 2 g/dl (3.1 +/- 0.1 g/dl; range, 0.1-6.8 g/dl) in 106/131 patients (81%) after an additional 2 months of CAB with concurrent XRT. The decrease in Hb levels paralleled the decreased in testosterone levels. No evidence of blood loss or hemolysis was found. CONCLUSIONS: There was no association between incidence or rate of Hb decrease and race, age, or pretreatment prostate-specific antigen (PSA) levels. However, the recovery from anemia after completion of CAB in African-Americans was slower than in Whites in the Z+ group (P < 0.04). Whereas grade 1 hematologic toxicity may occur in < 5% of the patients with zoladex alone, and approximately 6% with flutamide alone, in our study 81% showed mild to pronounced anemia. Since anemia has not been observed after treatment with XRT alone or XRT followed by zoladex, we conclude that the anemia was due to CAB. Recognition of this side effect should avoid unnecessary diagnostic evaluations.

A study of oral etoposide, infusional cisplatin, and infusional 5-fluorouracil for locally advanced or metastatic non-small-cell lung cancer. A Mid-Atlantic Oncology Program study.

A combination of oral etoposide, infusional cisplatin (24-hr) and infusional 5-fluorouracil (5-day) was used to treat 87 patients with non-small-cell lung cancer in a Phase II trial. Twenty-six patients were Stage IIIB, and 61 patients were Stage IV (new international classification). The regimen was well tolerated, with 49% grade 3 or 4 toxicities of all types. Response rates, partial and complete, were 40%, (95% confidence interval: 30%, 51%) for Stage IV patients and 20% (95% confidence interval: 10%, 32%), in Stage IIIB. An additional 68% of patients in Stage IIIB and 45% of patients in Stage IV achieved stable disease and had a median survival of 8.8 months, similar to that of patients in partial remission. Median survival was 5.6 months (95% confidence interval: 4.4 months, 10.8 months) for Stage IV patients and 11.0 months (95% confidence interval: 8.8 months, 12.4 months), for Stage IIIB. Of interest was the finding of a higher response rate in patients with a shorter duration of symptoms (less than 6 months versus greater than 6 months).

A study of infusional cisplatin and infusional fluorouracil for locally advanced or metastatic non-small-cell lung cancer: a Mid-Atlantic Oncology Program study.

A combination of cisplatin administered as a 24-hour infusion and fluorouracil administered as a 5-day infusion was used to treat 97 patients with non-small-cell lung (NSCLC) cancer in a phase II trial. Thirty patients had stage IIIB disease; 67 patients, stage IV disease (new international classification). Patients with stage IIIB disease also received thoracic radiation after chemotherapy. The regimen was well tolerated, with 24% or less grade 3 or greater toxicities of all types. One toxic death was attributed to fluid overload. The response rate, partial and complete, was 43% (95% confidence interval, 27% to 63%), and median survival was 13.8 months for patients with stage IIIB disease. Response rates refer to the chemotherapy response. For patients with stage IV disease, the response rate was 34% (95% confidence interval, 24% to 47%), and median survival was 6.2 months. On this regimen, stable-disease patients with stage IV disease had survivals at least equal to responders.

A prospective study of treatment techniques to minimize the volume of pelvic small bowel with reduction of acute and late effects associated with pelvic irradiation.

The volume, distribution, and mobility of opacified pelvic small bowel (PSB) were determined by fluoroscopy and orthogonal radiographs in 150 consecutive patients undergoing pelvic irradiation. Various techniques including uteropexy, omental transposition, bladder distention, inclining the patient, and anterior abdominal wall compression in the supine and prone treatment position were studied for their effect on the volume and location of small bowel within the pelvis. Abdominal wall compression in the prone position combined with bladder distention was selected for further investigation because of its simplicity, reproducibility, patient comfort, and ability to displace the small bowel. Factors correlating with the volume of pelvic small bowel (PSB) included prior pelvic surgery, pelvic irradiation (XRT), and body mass index. After pelvic surgery, especially following abdominoperineal resection (APR), there was a greater volume of PSB which was also less mobile. The severity of acute gastrointestinal effects positively correlated with the volume of irradiated small bowel. Overall, 67% of patients experienced little or no diarrhea, 30% developed mild diarrhea, and no patient required treatment interruption. Late gastrointestinal effects correlated with the prior pelvic surgery and with the volume of small bowel receiving greater than 45 Gy. Small bowel obstruction was not observed in 75 patients who had no previous pelvic surgery. However, following pelvic surgery excluding APR, 2/50 patients and following APR, 3/25 patients developed small bowel obstruction.

Small cell lung cancer: analysis of treatment factors contributing to prolonged survival.

Seventy-one consecutive patients with small cell lung cancer (SCLC) were treated in the Radiation Oncology Branch of the National Cancer Institute using six different radiation regimens in combination with cyclophosphamide, vincristine and doxorubicin chemotherapy. Patients treated with concurrent chemotherapy-irradiation (CT-RT) experienced better local tumor control than patients treated with sequential CT-RT. Maximum survival with minimum toxicity occurred in the group given a three-week course of concurrent CT-RT. Although concurrent therapy appeared more toxic than sequential therapy, it also appeared to result in more effective tumor control. Precise details of the timing of CT and RT represent important variables in study design of combined modality therapy for SCLC. Carefully controlled clinical trials should be undertaken to define the optimal timing and sequencing of CT-RT, as well as the optimal dose of RT.

Acute non-lymphocytic leukemia and acute myeloproliferative syndrome following radiation therapy for non-Hodgkin's lymphoma and chronic lymphocytic leukemia: cytogenetic studies.

Seven cases of acute nonlymphocytic leukemia (ANLL) and one of malignant myeloproliferative syndrome were identified from a pool of 189 cases of non-Hodgkin's lymphoma (NHL) and CLL treated primarily with extensive radiotherapy at the Clinical Center, the National Institutes of Health. Four patients also received chemotherapy, two for only short periods. The median time interval from the diagnosis of the primary malignancy to the development of leukemia was 61 months (range 33 to 98 months) and the median survival after the diagnosis of leukemia was two months (0 to 9 months). All eight patients were cytogenetically abnormal and serial chromosome studies revealed that hypodiploidy was the most commonly observed chromosomal abnormality. Abnormalities of chromosome no. 7 were seen in all five patients analyzed by the chromosome banding technique; four of them had monosomy 7. The next most frequently involved chromosome was no. 5. The complexity, extensive nature, and long duration of the cytogenetic abnormalities prior to the diagnosis of leukemia in these patients may be characteristic of secondary leukemia in radiation-treated lymphoma and the presence of such anomalies may predict leukemic transformation.

Acute nonlymphocytic leukemia and acute myeloproliferative syndrome following radiation therapy for non-Hodgkin's lymphoma and chronic lymphocytic leukemia: clinical studies.

Seven cases of acute nonlymphocytic leukemia (ANLL) and one case of a malignant myeloproliferative syndrome have been seen after extensive radiation therapy for non-Hodgkin's lymphoma or chronic lymphocytic leukemia. A myeloproliferative syndrome with abnormalities in granulocytic, erythrocytic, and thrombocytic cell lines was present in all patients and in seven patients preceded ANLL by 2--18 months. The median time to the development of ANLL after primary disease therapy was 61 months (33--98 range). The leukemia was extremely refractory to therapy and median survival after diagnosis of ANLL was two months (range 0--9 months). Leukemia was seen only in those patients who received multiple courses and multiple techniques of radiation therapy.

Surgical repair of esophagobronchial fistula following successful treatment of Hodgkin's disease.

A 33-year-old man with stage III-BS nodular sclerosing Hodgkin's disease received combination chemotherapy and subsequently developed a right middle lobe infiltrate in the lung unresponsive to antibiotic therapy. Thoracotomy revealed an esophagobronchial fistula with no evidence of malignancy. Surgical correction of the fistula was technically difficulty but proved lifesaving for this patient.

A comparison between combination chemotherapy and total body irradiation plus combination chemotherapy in non-Hodgkin's lymphoma.

Thirty-nine untreated patients with either lymphocytic or nodular mixed/nodular histiocytic non-Hodgkin's lymphoma, stage II--IV, were randomized to treatment with total body irradiation (TBI), 100 rads in 10 fractions over 12 days, plus combination chemotherapy with either cyclophosphamide, vincristine and prednisone (CVP) or cyclophosphamide, vincristine, procarbazine and prednisone (C-MOPP) or to treatment with combination chemotherapy (CVP or C-MOPP) alone. Remission rate and duration was comparable for both treatment groups; thus the use of both treatment modalities ab initio provides no therapeutic advantage.

Role of peritoneoscopy in the postoperative evaluation and treatment of adenocarcinoma of the exocrine pancreas.

Our experience with peritoneoscopy in the postoperative staging and evaluation of ten patients with locally unresectable adenocarcinoma of the exocrine pancreas is presented. In contrast to the German experience with previously unexplored patients, the pancreas was visualized only 30% of the time and biopsy was not possible for technical reasons. Based on our experience in these ten patients, postoperative peritoneoscopy for staging or for following the effectiveness of treatment is of limited value in carcinoma of the pancreas. Preoperative evaluation of this technique deserves greater attention.

Gallium scans for staging small cell lung cancer.

The high incidence of gallium 67 accumulation in lung cencer has made radioistope scanning with this agent useful in identifying the extent of cancer locally. However, we investigated the usefulness of whole-body gallium 67 scanning, compared with physical examination, bone, liver and brain scans, and bone marrow aspirate and biopsy, in detecting metastases outside the chest in 47 patients with small cell lung cancer. In each case whole-body scanning with gallium 67 was inferior to the other methods used to detect extrathoracic tumor deposits.

Cardiac candidiasis in cancer patients.

Histologically proven infection of the heart by Candida organisms occurred in 17 (10%) of 168 cancer patients with candidiasis studied at necropsy. All 17 patients were among the 85 patients with disseminated Candida infection; none of the 83 patients with localized candidiasis had involvement of the heart. Abscesses in the myocardium were present by histologic examination in all 17 patients and in 8 were evident on gross inspection as well. The mural endocardium was also affected in 5 patients from direct extension of a myocardial abscess. The valves were uninvolved. Pericardial infection was detected in 2 patients. The 17 patients with cardiac Candida infection had a higher frequency of positive premortem blood and cerebrospinal fluid cultures and of presence of Candida in the heart's blood than did the 68 patients with disseminated candidiasis but without involvement of the heart. Symptoms or signs of cardiac dysfunction resulting from the cardiac Candida infection were not readily detected in any patient. The clinical and pathologic features of cardiac candidiasis in cancer patients are distinct from those observed in Candida endocarditis.

"Total" therapy for small cell carcinoma of the lung.

Seventy-one consecutive patients with small cell carcinoma of the lung were treated with an integrated approach between November, 1974, and May, 1977. The regimen included radiotherapy to the primary site, relatively brief (6 to 12 weeks) although intensive chemotherapy, and prophylactic cranial irradiation. Complete responses were achieved in 75% and 40% of patients with limited and extensive disease, respectively. Modest prolongation of survival (median, 10 months) was realized by patients with extensive disease, but prolonged relapse-free survival was not observed. In contrast, one-half of the patients with limited disease who achieved a complete response have remained clinically free of disease without further treatment for a mean of 18 months (range, 6 to 33 months). Since all relapses to date have been noted within the first year following cessation of treatment, this experience suggests there may be a potential for cure in those survivors who are now relapse free for intervals exceeding two years.

Advanced lymphocytic lymphoma: randomized comparisons of chemotherapy and radiotherapy, alone or in combination.

Ninety-nine previously untreated patients with stage III and IV malignant lymphoma were randomized to receive either cyclic combination chemotherapy (50 patients) or extensive "systemic" radiotherapy (49 patients). Histologic classification included nodular poorly differentiated lymphoma (54 patients), nodular mixed lymphoma (21 patients), and diffuse poorly differentiated lymphoma (24 patients). High overall response rates were seen with either approach (90% for radiotherpy; 86% for chemotherapy) and complete remission were relatively common (60%--80%). Overall median survival of all patients in this trial will exceed 5 years regardless of the induction therapy used; however, disease-free survival is not commonly achieved with either regimen. Relapse-free survival rates at 4-year followup, regardless of induction regimen, are 13% for diffuse lymphomas and 24% for nodular lymphomas. The second prospective trial attempts to use a combined approach and compares cyclic combination chemotherapy with total-body irradiation and combination chemotherapy. Initial results on 34 patients indicate high overall response rates (100%) and similar complete remission rates (64%--67%). With 14 months' median followup no patients in either arm of the trial have died but relatively equal numbers have relapsed.