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Background: The cost of infusional administration of cancer chemotherapy has been assumed to be more expensive than the traditional bolus schedule related to the use of durable medical equipment and other components of the delivery system. The objective was to develop a model of projected charges as a basis for the cost estimate for selected common chemotherapy regimens comparing the cost based on charges for bolus and infusional chemotherapy schedules., Methods: Chemotherapy programs using either bolus or infusional delivery were selected representing standard or commonplace regimens for the treatment of patients with breast cancer (cyclophosphamide, methotrexate, fluorouracil [CMF] or CA); colon cancer (5-fluorouracil[5-FU] infusion vs. 5-FU bolus + leucovorin [LCVI] or lymphoma (cyclophosphamide, hydroxydaunomycin, Oncovin (vincristine), prednisone [CHOP] or CDE [cyclophosphamide, doxorubicin, etoposide]). Cost projections were estimated based on charges and were calculated in a model system using six charge (cost) centers including medical doctor [MD] and/or clinic visit; laboratory; drug cost based on average wholesale price (AWP); cost of disposables; and pump rental fee. Standard dosages were applied for each regimen using total mg/M2 for a 1.5 M2 person., Results: Projected charges or chemotherapy for colon cancer (5-FU infusion vs. 5-FU + LCV) are variable depending on the LCV dose and the infusion duration. The longer infusion duration or higher doses of LCV result in a 40 to 50% increment in monthly charges excluding cost related to toxicity. For breast cancer, the charges for bolus or infusion administration CMF are similar, but for CA bolus charges are higher than infusion charges related to higher drug doses. For lymphoma, CHOP chemotherapy dosage costs are approximately half of those for CDE infusion related to the specific drug regimen and drug dosage used., Conclusions: The perception that infusional delivery of chemotherapeutic agents adds to the cost of cancer care is appropriate for some regimens but the absolute amount of cost increment is generally modest. The principle cost differences between bolus and infusional schedules relate to drug dosage and the toxicity profile. Generally, but not consistently, infusional schedules use lesser doses and are associated with lesser toxicity. Although the benefit of infusional delivery of chemotherapy in terms of response rates and survival are comparable to bolus schedules for 5-FU infusion and 5-FU + LCV in colon cancer, this has not been established for the regimens analyzed for breast cancer (CMF, CA) or lymphoma (CDE, CHOP). The misperception of cost advantages for bolus delivery should not preclude comparative trials of bolus versus infusional chemotherapy schedules and cost should be studied prospectively in clinical trials comparing different schedules of administration in addition to studies of quality of life and toxicity.

Three patients developed bilateral breast cancer at 10 to 24 years after mantle irradiation for locally or systemically advanced Hodgkin's disease (HD). Four of the six cancers in the three patients were detected only by mammography. Pathologically, five of the cancers were intraductal carcinomas (four with an invasive component) with one being a lobular carcinoma. Five of the six lesions were Stage I pathologically without evidence of axillary nodal involvement. It is recommended that female patients with Hodgkin's disease who have received mantle irradiation as part of the therapy for their Hodgkin's disease and who are observed for 10 or more years after completion of mantle irradiation be considered at risk for the development of breast cancer. Such patients should be monitored appropriately by routine bilateral mammograms to increase the early detection of early stage lesions.

2 patients with metastatic cancer (Ewing's sarcoma and breast cancer) developed pleural effusions while undergoing systemic therapy for pulmonary metastases. Thoracenteses failed to reveal malignant cells and in both instances the characteristics of the fluids were those of transudates. The effusions developed in association with dissolution of pulmonary lesions and presumably represent a reactive process to tumor regression.

Five patients with breast cancer and malignant melanoma are reported. Two patients had a third primary malignancy. In 4 out of 5 patients the breast tumor was the initial tumor discovered, and in 4 out of 5 the second tumor evolved metachronously. No specific carcinogenic factor could be established. The low malignancy potential of the melanoma by pathologic criteria may explain the lack of previous reports of this association.

Two patients with squamous cell carcinoma of the breast are described. In one patient the lesion represented a primary breast tumor; in the second, a metastases from primary bonchogenic carcinoma. Neither lesion possessed estrogen receptor protein. This report emphasizes the rarity of epidermoid lesions of the breast and the importance of identifying an extramammary primary source of metastases to the breast.

Serial measurements of plasma carcinoembryonic antigen (CEA) levels were analyzed in 42 patients with advanced breast cancer undergoing systemic chemotherapy. Pretreatment CEA levels exceeded 5 ng/ml in 22 patients, and 19 of 22 serial assays uniformly heralded tumor regression as well as subsequent tumor relapse. A significant quantitative alteration in CEA levels was established as a minimum change of 20% within 8 weeks of therapy. In 13 of 15 patients responding to chemotherapy and in all patients with CEA levels higher than 35 ng/ml, this criterion was not abrogated, and there were no discordant observations. Rising CEA levels were correlated with subsequent progression of disease in all patients with elevated baseline levels at a minimum of 8 weeks before the progression was clinically evident. In advanced breast cancer the effectiveness of therapy and the development of tumor resistance may be monitored by serial plasma CEA levels, and specific quantitative criteria should be applied.

The gross cystic disease fluid protein of 15,000 MW (GCDFP-15) has been demonstrated to be a circulating glycoprotein tumor marker for breast carcinoma in approximately 40% of patients with advanced disease. A recent retrospective analysis of plasma GCDFP-15 levels in patients with advanced breast cancer suggested that androgen therapy could cause significant increases in plasma levels in the absence of disease progression. In order to evaluate the frequency, time course, and intensity of the androgen effect on GCDFP-15 production, a prospective study was initiated. Twenty-nine patients with stage IV breast carcinoma were treated with fluoxymesterone (20 or 30 mg/d). Plasma levels of GCDFP-15 and carcinoembryonic antigen (CEA) were measured by radioimmunoassay before and at various times during therapy. By day 6 of therapy, plasma GCDFP-15 had increased significantly (p = 0.03) from a mean basal level of 58 +/- 12 ng/ml to 160 +/- 60 ng/ml. By contrast, the mean CEA levels in the same patients increased only from 36 +/- 14 ng/ml. The distribution of percent increases in plasma GCDFP-15 was not uniform, but patients with high (greater than 82 ng/ml) basal levels had marked (greater than or equal to 75%) increases in 6/6 (100%) cases, whereas patients with low (less than 30 ng/ml) basal levels had similar increases in only 2/15 (13%) cases. Urinary excretion of GCDFP-15 usually paralleled the increases in plasma levels of the glycoprotein during the first six days of therapy. A linear correlation between percent change in plasma and percent change in urinary GCDFP-15 was demonstrated. A permanent cell line of human breast carcinoma, T47-D, was stimulated to secrete GCDFP-15 in vitro by androgen, but not by estrogen. From these data, we conclude that androgens can specifically stimulate secretion of GCDFP-15 by breast carcinoma tissue in most patients with elevated plasma levels of GCDFP-15, and in some patients with normal levels. The stimulation occurs within days and is not associated with clinical signs of tumor growth.

Forty-three postmenopausal females with advanced breast cancer were studied in a prospective comparative trial of estrogen vs. an anti-estrogen (tamoxifen) therapy with a crossover to the alternative hormone with progressive disease. Ten of 19 patients (53%) responded to primary tamoxifen therapy and six of 24 (25%) responded to primary estrogen therapy. Crossover responses were observed in seven of 19 (37%) on the secondary tamoxifen therapy and in two of 10 (20%) on secondary estrogen therapy, and were not related to the response to the primary hormonal maneuver. Responses were related to the presence of estrogen receptor protein (ERP), particularly for tamoxifen therapy, although responses were observed in three of six ERP negative patients receiving estrogen and in seven of 25 (28%) of patients with an unknown ERP status. Complications were observed in 35 instances with estrogen therapy and in only five instances with tamoxifen therapy. Initial hormonal therapy with tamoxifen in postmenopausal patients with advanced breast cancer and ERP status positive or unknown is superior to primary estrogen treatment. Secondary therapy and response to estrogen or tamoxifen is not necessarily predicted by the initial hormone response, and crossover to the alternative therapy is generally indicated.

A randomized trial of Adriamycin (A) in combination with melphalan (M), (MA therapy), and in combination with M plus cyclophosphamide (C) (MAC therapy), was initiated in 40 evaluable patients with metastatic breast cancer. Twenty-two patients demonstrated an objective response to therapy: 9/20 to the MA regimen, and 13/20 to the MAC regimen. For the 22 responders, median duration of response is not yet achieved for either complete or partial responders, at 10 and 9 months, respectively. The addition of the two alkylating agents to Adriamycin was superior to the single alkylating agent addition, both in total response rate and in completeness of response. Maintenance therapy, after achieving the maximum cumulative dose of Adriamycin, was provided by cyclophosphamide plus methotrexate and 5-fluorouracil (CMF). In 19 patients completing induction and entering maintenance therapy, only one relapse has developed with maximun follow-up at 15 months.