In this case series we present a variety of different cardiac toxicities with 5-fluorouracil and its pro-drug capecitabine, including myocardial infarction, cardiomyopathy, sinoatrial and atrioventricular node dysfunction, takotsubo cardiomyopathy and QT prolongation with torsade-de pointes ventricular tachycardia. We stress the fact that while vasospasm is a well-recognized side-effect of this class of chemotherapeutic agent, broader cardiotoxicity is commonly seen and an increased awareness of the range of toxicity is necessary if repeat toxicity is to be avoided.

BACKGROUND The use of body surface area in determining chemotherapy dosing, particularly in the obese, remains controversial. Total body nitrogen (TBN) measurement in patients with serious illness has been suggested to be an accurate predictor of clinical course. The ability of TBN to predict chemotherapy‐induced neutropenia was examined in the current study. METHODS TBN measurements were performed in 31 female outpatients with breast carcinoma who were undergoing standard cyclophosphamide, methotrexate, and 5‐fluorouracil (CMF)‐based chemotherapy (median age, 48 years; range, 26– 77 years). TBN was measured using the in vivo neutron capture analysis technique on Day 1 of Cycles 2–6. The chemotherapy toxicity index used was the absolute neutrophil count nadir (ANCN). Neutropenia was defined as an ANCN < 1.0 × 109/L. The nitrogen index (NI) (TBN expressed as a percentage of age‐, gender‐. and height‐matched healthy patients) then was compared with the corresponding ANCN values. RESULTS Using receiver operating characteristics analysis, a “cut‐off” value of NI = 0.89 was found. In this group of patients, when the NI was < 0.89, 11 of 13 courses in 7 patients (85%) led to an ANCN of < 1.0 × 109/L, and when the NI was > 0.89, 29 of 109 courses (27%) led to an ANCN of < 1.0 × 109/L (P < 0.0001). CONCLUSIONS In this small group of breast carcinoma patients, the NI was found to be the most powerful predictor of neutropenia after CMF‐based chemotherapy. The authors conclude that NI may be a useful clinical tool in identifying patients at a higher risk of chemotherapy‐induced toxicity when widely distributed drug combinations such as CMF are used, and warrants further study with other commonly used drugs or drug regimens. Cancer 2000;88:796–803. © 2000 American Cancer Society.

Treatment options and prognosis remains poor for patients with recurrent glioblastoma multiforme. These tumors are highly vascularised and over express angiogenic factors such as vascular endothelial growth factor and may potentially be responsive to antiangiogenic therapies. We present the results of a phase II trial of Thalidomide, an antiangiogenic agent, in the treatment of recurrent glioblastoma multiforme. Patients were treated with 100 mg/day of Thalidomide, increased at weekly intervals by 100 mg to a maximum tolerated dose of 500 mg/d. Forty-two patients were enrolled, with 38 patients being assessable for response and 39 for toxicity. Two patients (5%) achieved a partial response and 16 (42%) had stable disease. The median survival was 31 weeks and the 1-year survival was 35%. Patients who had a partial response or stable disease had either a stabilisation or improvement in quality of life scores or performance status. Overall Thalidomide was well tolerated with no grade 4 toxicities and no treatment related deaths. The median maximum tolerated dose was 300 mg/day. The most common toxicity was fatigue to which patients developed tachyphylaxis. There was no correlation demonstrated with plasma vascular endothelial growth factor levels and response or survival. Thalidomide is a well-tolerated drug that may have some activity in the treatment of recurrent glioblastoma. Optimum dosing with antiangiogenic agents is currently under investigation. Chronic low dose therapy may be required to see conventional responses or improvements in time to progression. The dose required to achieve optimal biological impact may be better defined once we have established reliable surrogate endpoints.