Antonio Bianco

Treatment of breast cancer in older women

Background. Breast carcinoma management in the elderly often differs from the management in younger women and there is considerable controversy about what constitutes appropriate cancer care for older women. This controversy is reflected in the persistence of age-dependent variations in care over time, with older women being less likely to receive definitive care for breast cancer. There has been a significant increase in the last years in the number of studies conducted in older patients with breast cancer. Although available age-specific clinical trials data demonstrate that treatment efficacy is not modified by age, this evidence is limited by the lack of inclusion of substantial numbers of older women, particularly those of advanced age and those with comorbidities. Method. The literature-based evidence of the last 10 years was extensively reviewed on the main issues concerning the treatment of breast cancer in older women. Results.Surgical treatment in older patients has evolved from avoidance to mastectomy to breast-conserving surgery, similarly to younger patients. Given its negative effect on the quality of life, in the last few years the role of adjuvant radiotherapy has been questioned in elderly patients with breast cancer. Adjuvant chemotherapy benefit in older patients applies mainly to Estrogen-receptor-negative patients, while in Estrogen-receptor-positive patients a major role is played by endocrine treatment. New “elderly-friendly” drugs, that can help clinicians to reduce toxicity, are now available for breast cancer.

Secondary leukemia following treatment for Hodgkin's disease.

Aims and Background Patients treated for Hodgkins disease with chemotherapy or with the association of chemotherapy and radiotherapy have an increased risk of secondary leukemia. The aim of this study was to evaluate the leukemogenic risk due to these treatment modalities. Methods We performed a case-control study on a population of 1410 patients treated for Hodgkins disease from 1970 to 1990 in our Institute. Among these patients, we identified 25 cases of secondary leukemia and 3 cases of myelodysplasia, all occurring more than one year after the diagnosis of Hodgkins disease. Three cases occurred among the patients treated with radiotherapy alone. When we analyzed the risk in relation to the type of treatment (radiotherapy, chemotherapy, or both), the comparisons were relative to patients treated with radiotherapy alone. Results We found that chemotherapy alone is associated with a fivefold increased risk (odds ratio = 5.4) compared with radiotherapy alone. When both treatments are used, the risk is not further increased (odds ratio = 4.4). Patients receiving more than 6 courses of chemotherapy have an excess risk (relative risk = 2.5) compared with those treated with 6 courses or less. No increased risk was observed after splenectomy. Conclusions This study confirms an increased incidence of secondary leukemia occurring in patients treated for Hodgkins disease. The increased risk seems to be correlated with the number of courses of alkylating agent therapy, whereas it is unaffected by the addition of radiotherapy.

Epirubicin, methotrexate and bleomycin in the management of recurrent squamous cell head and neck cancer. A GSTTC randomised phase II study

53 patients with squamous cell carcinoma of the head and neck recurrent after initial treatment were entered into a phase II trial of the epirubicin, methotrexate and bleomycin (EMB) combination. The primary objective of the study was to evaluate the activity of this combination. Compliance to EMB and the possible non-cross-resistance to previous cisplatin-containing chemotherapy were secondary objectives. In order to avoid patient selection bias, the study involved randomisation between EMB and a cisplatin-methotrexate-bleomycin (DMB) combination (with EMB: DMB = 2:1). 23 out of 53 (43% +/- 13) EMB patients showed an objective response, lasting a median of 12 (range 4-39) weeks; interestingly, 5 out of 14 (36% +/- 25) patients pretreated with cisplatin plus 5-fluorouracil responded to EMB. The treatment compliance was good and a median of three courses was delivered. No patient refused the treatment after the initial cycle. Leukopenia (47%) and oral mucositis (42%) were the main side effects. DMB produced a response rate of 33% +/- 18 with a median duration of 5 (4-13) weeks. None of the patients previously treated with cisplatin plus 5-fluorouracil responded. 5 patients refused the treatment after the first cycle and a median of two cycles (0-5) was delivered. In conclusion, EMB produced results similar to cisplatin-containing regimens, with a mild to moderate toxicity and a good compliance; the possible non cross-resistance with cisplatin plus 5-fluorouracil deserves further evaluation.

TREATMENT OF ELDERLY CANCER PATIENTS: A PLANET IN EVOLUTION

ACKNOWLEDGMENTS The authors would also like to thank Dr. Ding Yew Yoong for his input on analysis. Financial Disclosure: None. Author Contributions: Ruth Chu-Ai Teh: study concept and design, acquisition of data, analysis and interpretation of data, preparation of manuscript. Wee Shiong Lim: study concept and design, analysis and interpretation of data, preparation of manuscript. Rohana Basri: acquisition of data. Noor Hafizah Ismail: analysis and interpretation of data. Sponsor’s Role: None.

Comment on: Incidence, pattern and timing of brain metastases among patients with advanced breast cancer treated with trastuzumab

We read with interest the article by Yau et al. focusing on incidence, pattern and timing of brain metastases among patients with advanced breast cancer (ABC) treated with trastuzumab [1]. This case series, like several other recent studies [2], reports frequent observation of central nervous system (CNS) recurrence during treatment with trastuzumab. We would like to stress these findings, reporting here our experience in 14 patients with ABC receiving trastuzumab and chemotherapy, with emphasis on neurological symptoms. Seven of 14 patients (50%) developed brain metastases and underwent a complete neurological evaluation. Table I synthesizes their main characteristics and outcome. Median time from the beginning of the treatment with trastuzumab plus chemotherapy to the diagnosis of brain metastases was 16 months (range 7 33). Several neurological symptoms were present, but, interestingly, headache was the most common neurological symptom indicative of CNS involvement at diagnosis (six of seven patients; 85%). At CT scan evaluation of the brain, only one patient had a single metastasis and none of the lesions showed signs of haemorrhage. Six patients received whole brain radiotherapy and one did not receive any treatment due to early death. Median survival was 6 months (range 1 11), calculated from the diagnosis of brain metastases. We agree with Yau and coworkers on the importance of having vigilant surveillance in asymptomatic patients. Physicians should also be aware of the possibility that symptoms related to CNS metastatic involvement can occur in the setting of a good control of neoplastic disease outside the CNS. When this happens, headache can represent an important early symptom. A constant, progressively increasing pain, or a change in the characteristics of

Treatment of non-Hodgkin's lymphoma in the elderly. The Italian studies.

Elderly patients constitute a significant proportion of patients with Non-Hodgkins Lymphoma (NHL). They generally have poorer prognosis than their younger counterparts. The International NHL prognostic factor project, although based on series of patients prevalently younger than 65 years, found that age is the most important prognostic factor. Inferior outcomes in elderly patients may result from the use of lower doses of chemotherapy and consequently poorer disease control, from increased susceptibility to the toxic effects of chemotherapy and more treatment related deaths, and from an increased prevalence of comorbidity with more deaths from causes unrelated to lymphoma. Apparently unrelated deaths can occur both on and off therapy. Two different therapeutic approaches have been adopted for elderly patients. The first one favors the use of standard treatments, unless severe comorbidity conditions are present. The second approach intends to utilize regimes specifically designed for elderly patients.