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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<.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 +/- standard error) is 79% +/- 2% for patients on the high-dose arm, 77% +/- 2% for the patients on the moderate-dose arm, and 72% +/- 2% for patients on the low-dose arm; disease-free survival is 66% +/- 2%, 61% +/- 2%, and 56% +/- 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. [ABSTRACT FROM AUTHOR]

Assessment of renal function prior to cisplatin chemotherapy has long been based on measurement of creatinine clearance by 24-hour urine collection (CrCmeas). Estimated creatinine clearance (CrCest) as calculated from the patient's age, weight, and serum creatinine level has been suggested as an adequate surrogate for CrCmeas, as it provides advantages of improved convenience, decreased cost, and possibly increased accuracy. We studied 847 patients receiving cisplatin-based chemotherapy on Cancer and Leukemia Group B (CALGB) protocols to determine whether the CrCmeas, CrCest, or serum creatinine value or the age of the patient would predict the subsequent genitourinary (GU) toxicity. Both CrCmeas (P = 0.001) and CrCest (P = 0.02) were predictive of subsequent grade 2+ GU toxicity, with CrCmeas being a slightly better predictor. Patient age also influenced subsequent GU toxicity, with the risk increasing with age (P = 0.0008). When patients were classified by age group and by CrCmeas, distinct subgroups were identified, with differences in the risk for grade 2+ GU toxicity ranging from 14% to 32%. Using a logistic model to assess the probability of grade 2+ GU toxicity, we found that an age of greater than or equal to 60 years (P = 0.005), a CrCmeas value of less than 75 ml/min (P = 0.004), and the risk characteristics of the individual cisplatin trial were important, whereas CrCest was not. Furthermore, CrCest proved to be a poor predictor of a CrCmeas value of less than 75 ml/min, "misclassifying" nearly half of the patients to a "lower-risk" subgroup. In summary, both CrCmeas and the patient's age independently provided predictive information concerning cisplatin GU toxicity. Our data support the continued clinical usefulness of determining the CrCmeas value prior to the administration of cisplatin-based chemotherapy to most patients. [ABSTRACT FROM AUTHOR]

A case of fatal dilated cardiomyopathy induced by esorubicin (ESO) at a total dose of 740 mg/m2, given in 27 doses over 650 days, is reported. The sudden onset, rapid clinical deterioration, and fatal outcome are detailed. The outcome was not predicted by serial rest ejection fractions or clinical signs. The data from animal studies, phase 1 and phase 2 clinical testing, are reviewed, demonstrating the almost complete absence of reports of ESO-induced cardiotoxicity. Studies reviewing ejection fractions and myocardial biopsy scores show that ESO can be cardiotoxic and may produce fatal dilated cardiomyopathy. [ABSTRACT FROM AUTHOR]

Hypersensitivity reactions from cytotoxic agents have not been accorded much attention. Certain drugs (L-asparaginase, cisplatin, intravenous melphalan, topical mechlorethamine, zinostatin, and teniposide) produce reactions often enough to be a clinical problem. Others (cyclophosphamide, doxorubicin, daunorubicin, methotrexate, and procarbazine) do so only occasionally. Bleomycin uniquely produces an occasional hyperpyrexic reaction with clinical findings similar to anaphylaxis. Some cytotoxic agents have never been known to produce hypersensitivity reactions. This paper reviews the frequency and clinical information about such reactions, factors augmenting or decreasing the frequency, and, where possible, the etiologic mechanisms. [ABSTRACT FROM AUTHOR]

A patient is presented who developed a diffuse mixed lymphoma after successful treatment of small cell undifferentiated carcinoma of the lung. The patient was treated with cytotoxic chemotherapy and irradiation for the lung cancer, and had no recurrence during 6 years with no treatment. He then developed stage IV lymphoma. The relationship between these two cancers and the occurrence of treatment-induced second malignancies in small cell carcinoma are discussed. [ABSTRACT FROM AUTHOR]

A patient is presented who developed nephrotoxicity after therapy with lomustine (CCNU) for astrocytoma of the brain. Only three other cases of lomustine nephrotoxicity have been reported, and all cases have been associated with cumulative drug doses of greater than 1,500 mg/m2. The clinical and pathologic features of lomustine nephrotoxicity are reviewed. It is recommended that cumulative doses of more than 1,200-1,4000 mg/m2 lomustine be avoided because of the risk of nephrotoxicity. [ABSTRACT FROM AUTHOR]