Autologous graft-versus-host disease induction in advanced breast cancer: role of peripheral blood progenitor cells.

The purpose of the present study was to investigate the impact of the use of peripheral blood progenitor cells (PBPCs) on the induction of autologous graft-versus-host disease (GVHD) in patients with advanced breast cancer. 14 women with stage IIIB and 36 women with stage IV breast cancer received cyclosporine (CsA) 2.5 mg kg-1 i.v. daily, d 0-28, and interferon-gamma (IFNg) 0.025 mg/m2 s.c. qod, d7-28, following PBPC-T +/- bone marrow transplantation (BMT). Preceding high-dose chemotherapy consisted of cyclophosphamide 6 g/m2 and thiotepa 800 mg/m2. Histologically proven > or = grade II cutaneous GVHD was induced in18/50 (36%) of patients and was independent of the source of haematopoietic support. In vitro studies showed that post-transplant, 76% of patients had developed auto-cytotoxicity against their own pre-transplant PHA-lymphoblasts. A significant correlation between the occurrence of GVHD > or = grade II and cytolysis was observed in the NK cell-line K562 and the T47D breast cancer cell-line. With a median follow-up of 2(1/2) years, the overall survival (OS) is 58%, the disease-free survival (DFS) 26%, both independent of the development of GVHD and similar to what has been observed in other studies on high-dose chemotherapy in advanced breast cancer. It therefore remains unclear whether the induction of autologous GVHD with the occurrence of auto-cytotoxic lymphocytes can result in an anti-tumour effect in this group of patients.

A prospective pharmacologic evaluation of age-related toxicity of adjuvant chemotherapy in women with breast cancer.

Despite increasing evidence of benefit from adjuvant chemotherapy, older women with breast cancer are commonly given less aggressive treatment than younger patients. Conflicting prior data regarding age-related toxicity prompted this prospective study. Forty-four women (aged 35-79 years) with early-stage breast cancer were treated with four cycles of adjuvant therapy with doxorubicin 60 mg/m2 i.v. and cyclophosphamide 600 mg/m2 i.v. every 21 days. They were monitored for myelosuppression, cardiotoxicity, and decrease in quality of life. Pharmacokinetics were analyzed using cycle 1 plasma samples. Bone marrow granulocyte and macrophage colony-forming units (CFU-GM) were assayed in vitro for dose response to 4-hydroperoxycyclophosphamide and doxorubicin before cycle 1. There was moderate evidence of age-related decrease in nadir absolute neutrophil count (ANC) when age was viewed as a continuous variable. On average there was a 10/microliter drop in cycle 1 nadir ANC for every year increase in age (p = 0.02). However, when age was viewed as a categorical variable (age < 65 vs. > or = 65 years), a similar proportion of women in each group reached an ANC < 100 (18% vs. 19%). Neither neutropenic complications, alteration in cardiac function, nor change in quality of life scores were significantly age related (p > 0.12). Pharmacokinetic analyses did not demonstrate age-related differences in the clearance of either doxorubicin or cyclophosphamide (p > 0.8). Pharmacodynamic analysis of individual patient bone marrow progenitor cell sensitivity did not reveal any correlation with age (p > 0.48). In women undergoing adjuvant therapy for breast cancer, no clinically significant age-related trends in toxicity were observed. These data suggest that older age alone should not exclude patients from receiving adjuvant therapy with doxorubicin and cyclophosphamide.

A phase I/II study of vinorelbine, doxorubicin, and methotrexate with leucovorin rescue as first-line treatment for metastatic breast cancer.

PURPOSE: This study was performed to determine the maximum tolerated dose (MTD) and toxicity of vinorelbine when used in combination with doxorubicin and methotrexate with leucovorin rescue in women with metastatic breast cancer. METHODS: Enrolled in the study were 23 women with metastatic breast cancer who had not received prior chemotherapy for metastatic disease. Patients treated at the first dose level received vinorelbine 20 mg/m2 on day 1, doxorubicin 40 mg/m2 on day 1, methotrexate 100 mg/m2 on day 1 and leucovorin 20 mg orally every 6 h for six doses beginning on day 2. Treatment was repeated every 21 days. The vinorelbine dose was escalated by 5 mg/m2 for patients treated at subsequent dose levels. The MTD was defined as the dose level at which fewer than one-third of patients enrolled experienced dose-limiting toxicity (DLT). When the MTD of vinorelbine had been determined, the doxorubicin dose was then escalated by 10 mg/m2 with the vinorelbine dose held at its MTD. RESULTS: total of 98 courses of treatment (median of 4 per patient, range 2-8) were administered. The MTD of this regimen was found to be vinorelbine 25 mg/m2, doxorubicin 40 mg/m2, and methotrexate 100 mg/m2 with leucovorin rescue. At higher doses of vinorelbine, neutropenia, fatigue, arm pain, malaise, nausea and vomiting were dose-limiting. Higher doses of doxorubicin resulted in universal dose limiting neutropenia, and frequent nonhematologic DLT consisting of arm pain, malaise, stomatitis, nausea and vomiting. Amongst the 20 patients with measurable disease, there were 3 complete responses (15%, 95% confidence interval 3%-38%), 5 partial responses (25%, 95% confidence interval 9%-49%) and an overall response rate of 40% (95% confidence interval 19%-64%). The median survival was estimated to be 25 months from the start of chemotherapy. CONCLUSIONS: Vinorelbine at 25 mg/m2 can be safely administered with doxorubicin at 40 mg/m2 and methotrexate at 100 mg/m2 with leucovorin rescue. Response rates observed with this regimen suggest that this combination of chemotherapeutic agents may not be more effective than the combination of vinorelbine and doxorubicin.

Long term follow-up of women treated with 16-week, dose-intensive adjuvant chemotherapy for high risk breast carcinoma.

BACKGROUND: A Phase II study was performed evaluating the disease free and overall survival rates associated with a dose-intensive, 16-week, doxorubicin-based adjuvant chemotherapy regimen in women with breast carcinoma and > or = 10 involved axillary lymph nodes. METHODS: Eligible patients underwent staging with computed tomography and bone scanning and were treated with a 16-week, dose-intensive chemotherapy regimen, comprised of 8 2-week courses of cyclophosphamide, 100 mg/m2 orally, on Days 1-7; doxorubicin, 40 mg/m2 intravenously (i.v.), on Day 1; methotrexate, 100 mg/m2 i.v., on Day 1 with leucovorin rescue, 10 mg/m2, every 6 hours for 6 doses orally on Day 2; vincristine, 1 mg i.v. on Day 1; 5-fluorouracil (5-FU), 600 mg/m2 i.v., on Day 2 over 2 hours; and 5-FU, 300 mg/m2/day continuous i.v. on Days 8 and 9. Tamoxifen, 20 mg daily, was administered to patients with estrogen receptor positive tumors treated after October 1988. All patients were offered locoregional radiation therapy. RESULTS: Sixty-four women were treated on protocol. The median follow-up of 27 surviving patients was > 8 years at last follow-up. Three patients were lost to follow-up. The median time to progression was 54 months, the Kaplan-Meier estimate of event free survival at 5 years was 44% (95% confidence interval [CI], 31-56%), and the Kaplan-Meier estimate of overall survival at 5 years was 57% (95% CI, 44-69%). At 98 months the Kaplan-Meier estimate of freedom from recurrence was 31% (95% CI, 19-43%) and the Kaplan-Meier estimate of survival at 111 months was 36% (95% CI, 23-49%). CONCLUSIONS: Despite the use of dose-intensive, doxorubicin-based, adjuvant chemotherapy, and intensive staging prior to study entry, the results of the current study are similar to those of previous reports for standard dose chemotherapy and appear inferior to those reported for high dose therapy.

Quality of life and quality adjusted survival for breast cancer patients receiving adjuvant therapy. Eastern Cooperative Oncology Group (ECOG).

PURPOSE: The objective was to compare health related quality of life (QOL) in hormone receptor negative, node-positive breast cancer patients receiving adjuvant chemotherapy to determine whether a more intensive chemotherapy regimen has an adverse effect upon QOL that is not balanced by improvements in disease control or survival. Increased physical symptoms, including fatigue and the inconvenience of the dose intensive 16-week regimen, were expected to have a negative impact on QOL. DESIGN: QOL was measured in 163 patients, randomized to either a standard cyclophosphamide, doxorubicin and 5-flurouracil (CAF) or a 16-week multidrug regimen, using the Breast Chemotherapy Questionnaire (BCQ). The 30 item BCQ was self-administered prior to therapy, during therapy, and 4 months post treatment. RESULTS: BCQ scores decreased (worsened) more during therapy on the 16-week regimen, median change -1.4, than on CAF, median change -0.8 (p < 0.001). By 4 months post treatment, BCQ scores were higher than pre-treatment and equal in the two arms (CAF: 8.1 and 16 weeks: 8.2, p = 0.6). Over a period of 48 months, patients on the 16-week regimen averaged 1.4 fewer months of treatment with toxicity, 4.0 more months without symptoms and 0.7 fewer months post recurrence compared to patients on the CAF regimen. Given typical values for these health states, the gain in Q-TWiST observed for the CAF regimen during treatment shifted to the 16-week regimen after 1 year, with a gain of 2.0 to 2.4 months after 4 years. CONCLUSIONS: The hypothesized negative impact of the dose intensive 16-week regimen was confirmed by the BCQ assessments. However, Q-TWiST analysis suggests a small gain for the 16-week regimen. The later results should be interpreted with caution with the limited follow-up of 4 years.

Sixteen-week multidrug regimen versus cyclophosphamide, doxorubicin, and fluorouracil as adjuvant therapy for node-positive, receptor-negative breast cancer: an Intergroup study.

PURPOSE: The Intergroup conducted this breast cancer adjuvant trial to compare an investigational 16-week regimen with cyclophosphamide, doxorubicin, and fluorouracil (5-FU; CAF). The 16-week regimen features greater doxorubicin and 5-FU dose-intensity than CAF and improved scheduling of antimetabolites with sequential methotrexate and 5-FU, as well as infusion 5-FU. PATIENTS AND METHODS: A total of 646 node-positive, receptor-negative patients were randomly assigned to receive either the 1 6-week regimen or six cycles of CAF. Breast cancer outcomes included recurrence as well as disease-free and overall survival. Toxicity was evaluated by the Common Toxicity Criteria (CTC). Treatment-related quality of life was assessed by the Breast Chemotherapy Questionnaire (BCQ) before, during, and 4 months after treatment in 163 patients. The trial was designed to use one-sided tests of significance for power calculations, but is now reported with both one-sided and the traditional two-sided tests of significance. RESULTS: At a median follow-up of 3.9 years, the estimated 4-year recurrence-free survival rate was 67.5% with the 16-week regimen versus 62.7% with CAF (P = .19, two-sided; P = .095, one-sided). The estimated 4-year survival rate was 78.1% with the 16-week regimen versus 71.4% with CAF (P = .10, two-sided; P = .05, one-sided). CAF produced significantly higher grades of leukopenia, granulocytopenia, and thrombocytopenia, as well as liver and cardiac toxicity, whereas the 16-week regimen produced significantly higher grades of anemia, nausea, stomatitis, and weight loss, as well as skin and neurotoxicity. There were three treatment-related deaths with CAF but none with the 16-week regimen. During treatment, quality of life declined significantly more with the 16-week regimen than CAF, but by 4 months posttreatment, there was no difference. CONCLUSION: The 16-week regimen produced marginally better breast cancer outcomes than CAF with similar toxicity but a greater reduction in during-treatment quality of life. The 16-week regimen should not be used instead of a standard-dose regimen without careful consideration of the 16-week regimen's pros and cons, which include its complicated schedule. It should probably not be tested further, but its antimetabolite schedules and frequent drug administration (ie, dose density) should be considered in the development of new regimens.

The effect of aging on the utilization of chemotherapy for metastatic breast cancer: a population-based study.

Older women (i.e., > or = 65 years of age) receive less adjuvant chemotherapy than younger women, in part because chemotherapy has been less effective in postmenopausal than premenopausal women in clinical trials. Metastatic breast cancer, however, does not respond differently to chemotherapy by age. Therefore, to evaluate further the effect of age on chemotherapy utilization, we conducted a population-based study of the treatment of metastatic breast cancer. Patients (n = 132) were identified by cross-tabulating death certificates from 1984 to 1991 with breast cancer cases in the Washington County Cancer Registry. Treatment information was obtained from the Tumor Registry of the Washington Country Hospital and Hospital medical records. Forty patients (74%) < 65 years old received chemotherapy compared to 11 (42%) 65-74 and 6 (12%) > or = 75 (p < 0.0001). Adjusting for other medical conditions and whether or not the patient saw a medical oncologist, there was still a significant effect of age in patients > or = 75 (p < 0.001) and a trend (p = 0.17) for patients 65-74. The different patterns of chemotherapy utilization were not associated with survival differences. Radiation therapy was also utilized significantly less frequently in older than younger patients, but the age effect was not as pronounced as with chemotherapy. There was no age effect on the utilization of hormonal therapy. Less frequent utilization of chemotherapy in older patients is probably caused by a combination of patient and physician factors and may result in less effective palliation for older patients.

Use of hematopoietic colony-stimulating factors: the American Society of Clinical Oncology survey. The Health Services Research Committee of the American Society of Clinical Oncology.

PURPOSE: Dissemination of use of the hematopoietic colony-stimulating factors (CSFs) is unprecedented in oncology, with almost all physicians having experience with granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) shortly after the drugs received Food and Drug Administration (FDA) approval in 1991. The American Society of Clinical Oncology (ASCO) Health Services Research Committee sought to assess patterns of use of CSFs before dissemination of its first-ever publication of ASCO guidelines. METHODS: A questionnaire describing clinical scenarios was mailed to American oncologists and hematologists who practice medical oncology. In each scenario, the physician was asked whether he would prefer to use a CSF to prevent or treat neutropenia. RESULTS: The response rate to the mailed survey was 49% (N = 475). Most physicians preferred to use CSFs for secondary prophylaxis in patients receiving chemotherapy at rates of 44% to 85%, rather than reduce doses. Patterns of use did not differ for palliative, curative, or adjuvant chemotherapy. While the majority of CSF patterns of care were similar to those recommended in the ASCO guidelines, more than half of the physicians chose to use CSFs in the treatment of febrile neutropenia, an area not supported in the subsequent guidelines. In general, physicians at academic medical centers and in Health Maintenance Organization (HMO) practices were more likely to prefer dose-reduction strategies over addition of CSFs, while fee-for-service physicians preferred the opposite strategies. CONCLUSION: Variations in CSF preferences for use were related to differences in clinical characteristics (history of afebrile v febrile neutropenia), drug characteristics (G-CSF or GM-CSF), and physician practice characteristics (HMO or fee-for-service setting). However, before dissemination of the guidelines, the majority of American oncologists preferred strategies that were subsequently included in the ASCO CSF guidelines. CSF guidelines would be most likely to reduce CSF use for treatment of afebrile and uncomplicated febrile neutropenia.

Prevalence of menopausal symptoms among women with a history of breast cancer and attitudes toward estrogen replacement therapy.

PURPOSE: To determine the prevalence and severity of vasomotor, gynecologic, and other symptoms among breast cancer patients, their health concerns, beliefs about estrogen replacement therapy (ERT), and willingness to take estrogen under medical supervision. MATERIALS AND METHODS: A questionnaire was mailed to 320 women aged 40 to 65 years and diagnosed with in situ or invasive locoregional breast cancer in the years 1988 to 1992. RESULTS: Of 222 eligible respondents, 190 were postmenopausal. The prevalence of symptoms among the postmenopausal women was as follows: hot flashes, 65%; night sweats, 44%; vaginal dryness, 48%; dyspareunia, 26%; difficulty sleeping, 44%; and feeling depressed, 44%. The latter two symptoms increased in frequency with increasing severity of vasomotor symptoms (P for trend < or = .001). Forty-one percent of menopausal women perceived that they had experienced, since their breast cancer diagnosis, a physical or emotional problem related to menopause. Of these women, 50% felt they needed treatment. Overall, 31% of postmenopausal women would consider taking estrogen. Those who perceived that they had experienced a menopausal problem were more likely to consider estrogen than those who did not (42% v 22%, P = .003). The proportions willing to take estrogen increased with increasing severity of symptoms, particularly feelings of depression and sleep disturbance (P for trend = .008 and .007, respectively). Awareness that estrogen decreases the risks of heart disease and osteoporosis was not associated with an increased willingness to take it. However, beliefs that estrogen increases the risks of recurrent breast cancer and uterine cancer were associated with a decreased willingness to take it (P = .003 and .08, respectively). CONCLUSION: Vasomotor symptoms have a significant impact on the quality of life of breast cancer patients. Clinical trials to determine the safest and the most effective ways to relieve these symptoms are needed.

A stopping rule for standard chemotherapy for metastatic breast cancer: lessons from a survey of Maryland medical oncologists.

The sequential administration of standard chemotherapy regimens to treat metastatic breast cancer may keep patients and oncologists from considering other important, but more psychologically difficult, issues such as the patient's declining health or approaching death. This practice also utilizes health care resources for ever-decreasing individual patient benefit. If generally agreed-upon rules or guidelines were developed about stopping standard chemotherapy after a limited number of regimens, oncologists could recommend treatment discontinuation with greater confidence. Also, resources could be redirected. To inform the development of guidelines on when to stop chemotherapy for metastatic breast cancer, we surveyed fully trained Maryland medical oncologists about their knowledge and beliefs about chemotherapy for metastatic breast cancer. The survey instrument included open-ended questions and clinical vignettes. There was consensus about the value of first-line chemotherapy. Even though oncologists employed second-line chemotherapy, they were unenthusiastic about it. The frequent utilization of second-line regimens probably reflects an effort to offer marginal regimens to patients who want them. Based on these data, it is suggested that standard chemotherapy be stopped after breast cancer fails to stabilize or respond on a standard regimen. Patients who wish further treatment could be referred for investigational therapy if it is available and if they are eligible.

Sixteen week dose intense chemotherapy for inoperable, locally advanced breast cancer.

Up to 15% of women with breast cancer have locally advanced disease at diagnosis. The poor response of these patients to local therapy alone and the frequent development of disseminated disease suggest that early intensive systemic therapy may benefit these women. Twenty-four patients with non-metastatic, locally advanced, primarily inflammatory, inoperable breast cancer were treated with a 16-week dose-intense chemotherapy regimen as induction therapy. Treatment consisted of 8 repetitive 2-week cycles consisting of 100 mg/m2 cyclophosphamide orally D1-7, 40 mg/m2 doxorubicin intravenously (IV) D1, 1 mg vincristine IV D1, 100 mg/m2 methotrexate IV D1, 10 mg/m2 leucovorin every 6 hours for six oral doses D2-3, and 600 mg/m2 5-FU IV over 2 hours D2. A continuous infusion of 300 mg/m2 5-FU per day was given IV D8-9 of each 2-week cycle. After induction all patients had at least a partial clinical response and were operable; 9/24 (37%) achieved a clinical complete response. All patients underwent at least a simple mastectomy. Pathologic examination revealed no evidence of gross macroscopic tumor in 11/24 patients (46%) and no evidence of microscopic disease in 4/24 patients (17%). Seven of 24 patients (29%) had no microscopic disease in the breast. At a median follow-up of 45 months, there have been 10 relapses in the 24 patients treated with this induction regimen. The actuarial relapse-free survival at 5 years is 58%. Actuarial overall survival at 5 years is 75%. We conclude that this regimen is safe and well-tolerated and that the results of this therapy are sufficiently promising to warrant further study of this regimen in patients with locally advanced breast cancer.

Offering the option of randomized clinical trials to cancer patients who overestimate their prognoses with standard therapies.

We have shown that cancer patients' routine (and understandable) overestimations of their prognoses with standard therapy may inhibit their accrual to randomized clinical trials for which standard therapies are the alternative. Patients' appreciation of the rationale for a trial, and the potential benefit of trial participation, can only be enhanced if they understand their prognoses with standard therapy. However, clinical investigators may be reluctant to provide specific information that deflates patients' estimates of their prognoses. The routine withholding of information regarding the modest benefits of standard therapies may avoid patient distress, but such physician behavior is paternalistic and may deleteriously affect trial accrual. On the other hand, the routine communication of prognostic information will cause significant distress among patients and will perhaps be destabilizing to that minority of patients who would otherwise shun this information or truly cannot psychologically tolerate it. A middle ground between these extremes is the stepwise disclosure of potentially distressing information, wherein specific prognostical information is offered by physicians to patients and actually provided or communicated only after patients first understand the nature of it and then indicate their interest in receiving it. A practical disadvantage of this approach is its additional demand on physicians' time. Therefore, if impracticality is to be avoided and yet the approach fostered, clinical investigators might consider developing trial-specific, written or audiovisual materials for patient education about general background information. These could be employed prior to patient-physician dialogue and so enable physicians to focus on more sensitive subjects, such as prognosis with standard therapy.

Noradrenergic activity in anticipatory nausea.

Two studies were conducted to examine the hypothesis that noradrenergic activity is a cause of the anticipatory nausea associated with cancer chemotherapy. In the first study concentrations of plasma 3-methoxy-4-hydroxyphenyl-glycol (MHPG) on day 1 of cycle 5 of initial chemotherapy were significantly higher in patients with than without anticipatory nausea. To determine whether elevated MHPG reflected a clinically significant causative role for noradrenergic activity in anticipatory nausea, we conducted a randomized, double-blind, placebo-controlled, crossover trial of clonidine for anticipatory nausea. At a dose of clonidine that produced significant side effects and reductions of plasma MHPG, anticipatory nausea was improved only marginally. These studies do not support a causative role for noradrenergic activity in anticipatory nausea that can be reduced by clonidine with an acceptable therapeutic index.

Psychosocial aspects of breast cancer.

In the past year, there have been timely and important reports on psychosocial aspects of breast cancer screening. Noteworthy papers have also been published on the psychologic sequelae of mastectomy compared with breast conservation, quality-of-life-adjusted survival analysis with breast cancer adjuvant therapy, and the relative importance to patients with metastatic breast cancer of quality-of-life dimensions.

Factors affecting treatment decisions for a life-threatening illness: the case of medical treatment of breast cancer.

Despite notions that patients are now playing a more proactive role in directing their own health care, our study of breast cancer patients considering adjuvant therapy indicates that, at least for a life-threatening illness, patients still rely heavily on their physicians to make treatment decisions. Out of 100 patients, 80.0% accepted their physician's primary treatment recommendation. Using behavioral decision-making theory we examined why some patients chose to disregard the physician's treatment recommendation despite its importance within the decision-making process. The discriminant function analysis performed to examine the factors influencing acceptance or rejection of a physician's treatment recommendation identified two sets of factors. Factors related to the amount and specificity of information about treatments conveyed to the patients, and the strength of the treatment recommendation itself. Patients who did not accept their physician's treatment recommendation were told in more specific terms what the benefits of treatment would be; they also rated side effects of treatment to be more probable and more severe than patients who did concur with the physician's treatment recommendation. These patients also rated their physicians' treatment recommendations as less strong than other physicians'. Nonacceptor patients were also better educated and were more likely to be risk takers. This study supports the findings of other studies that patients want more specific disease and treatment information, but suggests that the provision of this information might lead to therapy decisions which diverge from physicians' recommendations.

Effect of patients' expectations of benefit with standard breast cancer adjuvant chemotherapy on participation in a randomized clinical trial: a clinical vignette study.

Patients frequently overestimate the benefit of standard breast cancer adjuvant therapy. This is due in part to vague doctor-patient communication. To examine how the doctor's description and patient's expectations of the benefit of standard therapy affect clinical trial participation, we randomized 282 female cancer patients to one of two versions of a clinical vignette describing a choice between standard cyclophosphamide, methotrexate, and fluorouracil (5FU) (CMF) and a randomized trial comparing CMF with cyclophosphamide, doxorubicin, and 5FU (CAF). The vignettes differed only on whether results with CMF were described verbally or numerically in terms of disease-free survival (DFS). After selecting CMF or the trial, patients estimated their 10-year DFS with CMF. Patients were randomized 3:1 to the verbal vignette. The trial was selected by 110 of 210 (52.4%) verbal vignette patients versus 25 of 72 (34.7%) numeric vignette patients (P = .01). Estimates of 10-year DFS with CMF varied considerably; many were inaccurate. When patients in the verbal vignette group were divided into thirds according to DFS estimate, 22 of 64 (34.4%) in the top third selected the trial versus 38 of 64 (59.4%) and 38 of 65 (58.5%) in the middle and bottom third, respectively (P = .005). Younger age, college education, and previous participation in a trial also predicted trial selection. Multivariate logistic regression suggested that the benefit expected from CMF was more important than how benefit was described in treatment selection. Assuring realistic patient expectations of standard adjuvant therapy benefit is likely to be important during discussion of clinical trials.

Phase II trial of menogaril as initial chemotherapy for metastatic breast cancer.

Eighteen women with metastatic breast cancer previously untreated with chemotherapy were entered on a phase II trial of intravenous menogaril, a new anthracycline derivative. Treatment was given at 140 mg/m2 on days 1 and 8 of each 28 day cycle. The most common toxicities were leukopenia in all patients and burning and phlebitis at infusion sites in 72%. Serial assessment of cardiac function by resting and stress gated blood pool scans showed temporary decrements in ejection fraction in only 2 patients (11%). The response rate to the therapy was 19% [95% CI 0-38%] including 1 complete and 2 partial responses. The median time to relapse among responders was 6.5 months. Mean survival in all patients entered was 15.8 months from date of entry. Menogaril at this dose and schedule has modest activity as first line therapy for metastatic breast cancer but also has significant marrow and local toxicity.