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Background: Both total dose and dose intensity of adjuvant chemotherapy are postulated to be important variables in the outcome for patients with operable breast cancer. The Cancer and Leukemia Group B study 8541 examined the effects of adjuvant treatment using conventional-range dose and dose intensity in female patients with stage II (axillary lymph node-positive) breast cancer. Methods: Within 6 weeks of surgery (radical mastectomy, modified radical mastectomy, or lumpectomy), 1550 patients with unilateral breast cancer were randomly assigned to one of three treatment arms: high-, moderate-, or low-dose intensity. The patients received cyclophosphamide, doxorubicin, and 5-fluorouracil on day 1 of each chemotherapy cycle, with 5-fluorouracil administration repeated on day 8. The high-dose arm had twice the dose intensity and twice the drug dose as the low-dose arm. The moderate-dose arm had two thirds the dose intensity as the high-dose arm but the same total drug dose. Disease-free survival and overall survival were primary end points of the study. Results: At a median follow-up of 9 years, disease-free survival and overall survival for patients on the moderate- and high-dose arms are superior to the corresponding survival measures for patients on the low-dose arm (two-sided P [is less than] .0001 and two-sided P = .004, respectively), with no difference in disease-free or overall survival between the moderate- and the high-dose arms. At 5 years, overall survival (average [+ or -] standard error) is 79% [+ or -] 2% for patients on the high-dose arm, 77% [+ or -] 2% for the patients on the moderate-dose arm, and 72% + 2% for patients on the low-dose arm; disease-free survival is 66% [+ or -] 2%, 61% [+ or -] 2%, and 56% [+ or -] 2%, respectively. Conclusion: Within the conventional dose range for this chemotherapy regimen, a higher dose is associated with better disease-free survival and overall survival. [J Natl Cancer Inst 1998;90: 1205-11]

This study reports on a patient with acute myelogenous leukemia (AML) in remission who had a series of 11 granulocytic sarcomas (chloromas or myeloblastomas) appearing periodically over a 29-month interval in a variety of anatomic sites without evidence of bone marrow recurrence. This isolated extramedullary recurrence of AML is distinctly unusual with only 24 cases described previously. This patient had the greatest number and longest reported interval of recurrent granulocytic sarcomas (GS) before bone marrow relapse. Furthermore, he represents the first case of a patient with GS presenting with both an 8;21 chromosomal translocation and neural cell adhesion molecule (CD56) expression. The authors hypothesize that these two abnormalities identified previously as predisposing factors to GS may, in fact, be synergistic for this phenomenon. His case and the review of the literature demonstrate some of the important clinical and management features of a patient who develops GS while in complete marrow remission from previous AML. Although highly sensitive to radiation therapy, the onset of granulocytic sarcomas is almost always followed by bone marrow relapse and should be treated with aggressive reinduction chemotherapy and local irradiation. Such therapy is associated with the longest interval of disease-free survival.

Background. Survivors of advanced Hodgkin disease, who were assigned randomly to treatment by mechlorethamine, vincristine, procarbazine, and prednisone (MOPP); doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD); or MOPP alternating with ABVD in a clinical trial of the Cancer and Leukemia Group B (protocol 8251), were compared in terms of their psychosocial adaptation and psychosexual function an average of 2.2 years after completion of treatment (range, 1-5 years). The study was undertaken to determine if there were differences among treatments in these functional areas as a consequence of differential long-term gonadal damage in the three regimens. Methods. Ninety-three disease-free survivors of advanced Hodgkin disease (56 men and 37 women) were studied (a minimum of 1 year after completion of treatment) by an interview conducted over the telephone. Standardized measures were used to assess their psychologic, sexual, family, and vocational functioning, including the following tests: the Psychosocial Adjustment to Illness Scale--Self Report, the Brief Symptom Inventory, the Profile of Mood States, and the Impact of Event Scale. Results. Contrary to expectation, no statistically significant differences in survivors' psychosocial adaptation or psychosexual function were found by treatment arm. Infertility (based on survivors' reports of medical test results and perceptions) and lower income 1 year before the diagnosis of cancer were significant predictors of poorer adjustment. Most survivors reported a range of problems that they attributed to having had cancer: 35%, proven or perceived infertility; 24%, sexual problems; 31%, health and life insurance problems; 26%, a negative socioeconomic effect; and 51%, conditioned nausea, associated with visual or olfactory reminders of chemotherapy. Conclusions. No significant long-term advantage in psychosocial adaptation or psychosexual function was found for survivors of Hodgkin disease treated by the less gonadally toxic ABVD regimen 1 to 5 years after completion of treatment. Cancer 1992; 70:2508-2516.

Background. The long-term psychosocial adaptations of 273 survivors of advanced Hodgkin disease were assessed to determine the nature and extent of problems experienced and to identify those at high risk for maladaptation. Methods. Hodgkin disease survivors were identified who initially had been treated in clinical trials within the Cancer and Leukemia Group B from 1966 to 1986, were currently disease free, and had completed treatment for a minimum of 1 year. All survivors had advanced Hodgkin disease (with disease diagnosed at a mean age of 28 years). Survivors were at a mean age of 37 years at the time of interview (6.3 years after treatment completion), and 60% were male. Survivors were interviewed over the telephone 7-10 days after questionnaires were mailed to them concerning their psychological, social, vocational, and sexual functioning. Results. Psychological distress was found to be elevated by one standard deviation (SD) above that of healthy subjects on the Brief Symptom Inventory, and 22% met the criterion suggested for a psychiatric diagnosis. In addition, the following problems were reported by survivors to be a consequence of having had Hodgkin disease: denial of life (31%) and health (22%) insurance, sexual problems (37%), conditioned nausea in response to reminders of chemotherapy (39%), and a negative socio-economic effect (36%). Survivors found to be at high risk for maladaptation were: men earning less than $15,000 per year or who were currently unemployed; unmarried individuals; those with serious illnesses since treatment completion; and those who were less educated. Conclusions. These findings suggest that including a routine assessment of these factors would help to target survivors in need of additional evaluation and treatment. Cancer 1992; 70:2214-2224.

Prostate cancer is extremely common among older men. In 1991, an estimated 122,000 new cases occurred in the US, and 32,000 men died from this disease. It is estimated that 70 percent of patients with prostate cancer will develop metastatic disease. This spread of prostate cancer to other organs, often bones, may be temporarily controlled, but, as is the case for many cancers, metastatic disease is rarely cured. Prostate cancer is sensitive to stimulation by male hormones, and therapy for metastatic prostate cancer is directed at removing this source of stimulation. This is accomplished by surgically removing the source of male hormones or by chemically interfering with the normal production of male hormones. Temporary tumor control may be achieved in 80 to 85 percent of cases, but overall survival is less than three years after treatment. A pilot study was conducted to evaluate the combination of hormonal treatment with standard chemotherapy. Fifteen patients were treated with leuprolide and flutamide, drugs that block the synthesis of male hormones (androgens) and interfere with their effects. Prior to the standard chemotherapy, the patients were primed with androgens. This priming stimulates the cancer cells which had been suppressed by the antiandrogen treatment; the idea is to catch them with the cytotoxic chemotherapeutic drugs just at they are starting to multiply again. Three patients achieved a complete response, that is, a disappearance of the symptoms of cancer, as a result of this treatment. Eight patients experienced a partial response, which is generally defined as a reduction in apparent tumor mass of at least 50 percent. The remaining four patients experienced stabilization of their cancer. The median time to disease progression among these patients was 31 months, and nine of the 15 patients are still alive after a median follow-up time of 42 months. The results of the present study were excellent and suggest that a larger trial of this combination of hormonal and chemotherapy is in order. (Consumer Summary produced by Reliance Medical Information, Inc.)

Ifosfamide and cyclophosphamide are closely related chemotherapeutic agents. Both are transformed into active alkylating agents by liver enzymes, and both compounds are degraded to form acrolein and chloroacetaldehyde. These two compounds are believed to account for some of the drugs' unwanted toxic effects. Since the toxic by-products are the same, it is not surprising that many of the toxic effects of ifosfamide and cyclophosphamide are similar as well. These include nausea, bone marrow suppression, hemorrhagic cystitis, and dysfunction of the gonads. With higher doses, an antidiuretic effect can occur, leading to low sodium, loss of hair, and damage to the heart muscle. However, although previous reports have associated cyclophosphamide with interstitial pneumonitis, an inflammation of the lungs, there have been no reports of a similar condition resulting from ifosfamide treatment. Now, however, the case of a 58-year-old woman illustrates that interstitial pneumonitis can be a complication of ifosfamide treatment, as well. The woman had developed chest pain and the presence of a poorly differentiated sarcoma was identified by removal a portion of the lung. She was given radiation treatment and was well for almost a year until scattered metastases appeared. The patient was placed on a combined chemotherapeutic regimen consisting of doxorubicin, dacarbazine, mesna, and ifosfamide. After the fifth cycle of chemotherapy the patient developed symptoms of interstitial pneumonitis. The patient was treated with prednisone, and improved temporarily, but ultimately her condition deteriorated and she died. Autopsy confirmed the diagnosis of interstitial pneumonitis. Now that ifosfamide is commercially available, physicians should be aware of the possibility of interstitial pneumonitis as a potential complication. (Consumer Summary produced by Reliance Medical Information, Inc.)

PURPOSE: Multiagent chemotherapy and chemohormonal therapy for breast cancer are associated with an increased risk for venous thromboembolic complications. We observed instances of arterial thrombosis in two studies of breast cancer involving multiagent chemotherapy for stages II and III disease. Our purpose in this study was to determine the incidence of this complication and whether it appeared to be related to the chemotherapy or was a random event. PATIENTS AND METHODS: Episodes of arterial thrombotic events were identified from record reviews of 1,014 assessable patients with breast cancer entered on two Cancer and Leukemia Group B protocols. Details of the kind of arterial event, when it occurred, the outcome, and the occurence of metastases were analyzed. RESULTS: Thirteen (1.3%) patients had an arterial thrombosis: six (5.3%) of 113 patients with state II disease and seven (0.8%) of 901 patients with state II disease. Four of these patients had a peripheral arterial thrombosis and nine had strokes (four were fatal). All these events occurred while the patients were receiving adjuvant chemotherapy. Only one additional arterial event (a stroke approximately four years later) has occurred in this patient group after chemotherapy was completed. CONCLUSION: Arterial thrombosis is also associated with multiagent chemotherapy in patients with breast cancer. The mechanism is unknown., Blockage of the arteries by clots, or arterial thrombosis, has been observed with increasing frequency in women receiving chemotherapy for breast cancer. The incidence of venous thrombosis during chemotherapy has already been established. To determine the incidence of arterial thrombotic events and whether or not they are related to chemotherapy, 1,014 women receiving these treatments were monitored. This group included 113 women with clinical stage III breast cancer and 901 women with stage II breast cancer and lymph node involvement. Of the stage II group, seven patients (eight percent) experienced a thrombotic event; four were peripheral thromboses (clots in a leg artery) and three were cerebral thromboses (strokes). Six of the stage III patients (six percent) experienced a stroke. The incidence of arterial thromboses in this group of chemotherapy patients is higher than would occur in a similar group of women with or without cancer. This conclusion is based on a statistical analysis of the frequency of arterial thrombosis in patients at several major medical centers. Chemotherapy for breast cancer is associated with an increased risk of arterial thrombosis, but the mechanism of this event is not known.