Metastatic breast cancer with liver metastases: a registry analysis of clinicopathologic, management and outcome characteristics of 500 women

SummaryIntroduction Breast cancer patients developing liver metastases have traditionally been considered to make up a poor prognosis group with median survival rates of less than 6 months. We retrospectively analysed clinicopathologic characteristics of 500 women with metastatic breast cancer and liver deposits upon administration of first-line chemotherapy in the 90s. We sought to examine the epidemiology, clinical course, outcome and prognostic factors of this cohort with the hope to identify changing patterns, facilitate cost-effective follow-up and rationalize therapy of these patients.Materials and methods Among 1426 metastatic breast cancer patients enrolled with the Hellenic Cooperative Oncology Group (HeCOG) chemotherapy registry from 1988 to 2004, 500 (35%) had liver deposits when first-line chemotherapy was administered and were the subject of this retrospective analysis. These patients had been treated with single-agent or combination chemotherapy either in the context of clinical trials or outwith trials according to standard HeCOG protocols.Results Median age at diagnosis was 54.5 years, with the majority of women being fit (Performance Status PS 0–1 76%), postmenopausal (53%) harbouring hormone-receptor positive (54%) invasive ductal, lobular or mixed carcinomas (76%). High-grade tumours were present in 35% of patients, while the extent of systemic relapse was confined to the liver plus none or one additional organ site in 59% of women. Half of the patients had received adjuvant chemotherapy and two-thirds relapsed later than 12 months from initial diagnosis of localized disease. First-line palliative chemotherapy included an anthracycline and/or a taxane in 88% of cases with an objective response rate of 34% (95% Confidence Interval CI: 29.1–37.5), while 79% of patients were able to proceed to second-line chemotherapy based mostly on non-anthracycline non-taxane containing regimens with objective responses seen in 16% of them (95% CI: 11.6–21.9). At a median follow-up of 47.5 months, disease progression occurred solely in the liver in one-third of patients and median overall survival was 16.3 months, with projected 5-year survival of 8.5%. Type of palliative chemotherapy was not a predictive factor for response, though non-anthracycline non-taxane regimens were associated with lower tumour regression rates. Positive hormonal receptor status of the primary, low histological grade, malignant relapse in the liver only or liver plus one organ site and good performance status were significant prognostic factors for improved outcome in univariate analysis, the latter two retaining significance in multivariate analysis as well.Conclusions In comparison to historical series, adjuvant therapy, stricter follow up and imaging technology advances result in earlier diagnosis of fitter breast cancer patients with low-volume hepatic and systemic relapse. Cost-effectiveness of close monitoring for early diagnosis of relapse should be further studied. With availability of effective modern chemotherapy, prolonged survival is feasible and aggressive multidisciplinary management of selected patients may be warranted.     

Combination of topotecan and cisplatin in relapsed patients with small cell lung cancer: a phase II study of the hellenic cooperative oncology group (HeCOG)

Purpose: To assess the safety and efficacy of a 3-day schedule of cisplatin and topotecan in patients with recurrent small-cell lung cancer (SCLC). Methods: Thirty-four relapsed patients were treated with cisplatin 20 mg/m² and topotecan 0.9 mg/m², both given on days 1–3 every 3 weeks, in a phase II study. Results: Complete response (CR) was achieved in two patients (6%), partial response (PR) in 4 (12%), stable disease in 6 (18%) and progressive disease in 14 (41%). Eight patients (23%) were non-evaluable for response. Among 21 sensitive patients, 2 (9.5%) achieved CR and 3 (14%) PR. Among 13 refractory patients, none achieved CR and only 1 (8%) PR. Median survival was 6.5 months for all patients, 7.8 for sensitive and 6.2 for refractory. Median time to progression (TTP) was 4.4 months for all patients, 5.9 for sensitive and 3.2 for refractory. Grade 3–4 toxicities included anemia (15%), thrombocytopenia (15%), neutropenia (42%), nausea/vomiting (3%), and alopecia (6%). No toxic death occurred. Conclusions: This 3-day schedule was well tolerated, produced modest response rates but good survival and TTP both in sensitive and refractory patients with relapsed SCLC.     

Lipid-lowering drugs and serum liver enzymes: the effects of body weight and baseline enzyme levels

The most important side effects of fibrate and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) treatment are hepatic toxicity and myopathy. Obese individuals may have higher levels of serum transaminases than their lean counterparts. The main purpose of this study was to examine the effects of statins and fibrates on liver enzymes in obese patients and to compare them with their effects on patients with various body mass indexes (BMI). Two hundred and sixty-three hyperlipidemic patients of both sexes aged 31-74 years were studied for 24 weeks. One hundred and three patients received fluvastatin (40 mg/day), 62 atorvastatin (10-20 mg/day), 45 micronized fenofibrate (200 mg/day), 44 ciprofibrate (100 mg/day) and nine patients received gemfibrozil (900 mg/day). Laboratory determinations were performed at baseline, after 8 weeks of treatment and at the end of the follow-up period. At baseline, obese patients tended to exhibit elevated liver enzymes more frequently than their lean counterparts (12 of 105 vs. 5 of 67). At the end of the study period, 11 obese, seven overweight and six lean subjects exhibited elevated liver enzymes. Twelve patients who experienced a moderate elevation of serum liver enzymes at baseline had their liver enzyme profile normalized at the end of the study. Furthermore, in 12 patients who had normal serum liver enzyme levels at baseline, abnormal levels of at least one enzyme were observed after 24 weeks of treatment. Fibrates and statins are safe drugs for the treatment of hyperlipidemia in obese patients as well as in those with moderately increased liver enzymes.     

Respiratory kinematics by optoelectronic plethysmography during exercise in men and women

Gender differences in resting pulmonary function are attributable to the smaller lung volumes in women relative to men. We sought to investigate whether the pattern of response in operational lung volumes during exercise is different between men and women of similar fitness levels. Breath-by-breath volume changes of the entire chest wall ( _CW) and its rib cage ( _Rc) and abdominal ( _Ab) compartments were studied by optoelectronic plethysmography in 15 healthy subjects (10 men) who underwent a symptom-limited ( W _peak) incremental bicycle test. The pattern of change in end-inspiratory and end-expiratory _CW ( _CW,EI and _CW,EE, respectively) did not differ between the sexes. With increasing workload the decrease in _CW,EE was almost entirely attributable to a reduction in end-expiratory _Ab, whereas the increase in _CW,EI was due to the increase in end-inspiratory _Rc in both sexes. In men, at W _peak tidal volume [ _T, 2.7 (0.2) l] and inspiratory capacity [IC, 3.4 (0.2) l] were significantly greater than in women [1.8 (0.2) and 2.6 (0.2) l, respectively]. However, after controlling for lung size using forced vital capacity (FVC) as a surrogate, the differences between men and women were eliminated [ _T /FVC 49 (3) and 45 (3) respectively, and IC/FVC 63 (2) and 65 (3) respectively]. All data are presented as mean (SE). In both men and women the contribution of the rib cage compartment to _T expansion was significantly greater than that of the abdominal compartment. We conclude that gender differences in operational lung volumes in response to progressive exercise are principally attributable to differences related to lung size, whereas compartmental chest wall kinematics do not differ among sexes.     

A phase II study of sequential docetaxel and gemcitabine followed by docetaxel and carboplatin as first-line therapy for non-small cell lung cancer

Our study involves a preliminary phase II trial, which evaluates the activity, feasibility and tolerability of a sequential combination of docetaxel and gemcitabine followed by docetaxel and carboplatin, as first-line treatment for inoperable NSCLC. Twenty-six chemo-naïve patients aged less than 75 years with histologically or cytologically confirmed unresectable stage IIIB, IV or relapsed post-operative metastatic NSCLC were included in the study. Gemcitabine 1,250 mg/m² was administered and was followed by docetaxel 65 mg/m². Treatment was administered on days 1 and 14 in a 28-day cycle for three consecutive cycles. If patients had no progressive disease after three cycles of chemotherapy, they received another three cycles of docetaxel 65 mg/m² followed by carboplatin AUC5 on day 1 in a 21-day cycle. Recombinant human granocyte colony-stimulating factor (rhG-CSF) was given prophylactically. In addition, all patients received standard pre- and post- treatment with oral dexamethasone. Response rates at three cycles were: 19% achieved a partial response (PR), 46% had stable disease (SD) and 23% had progressive disease. At six cycles, 8% of the patients maintained PR, 19% showed SD and 35% had progressive disease. The median time-to-disease progression was 6 months. The median survival time of patients was 10 months while, at the end of the first year, the patients who managed to get through the complete therapy (20 patients) had a survival rate of 38%. This detailed analysis of 20 patients showed that 80% of the patients survived for up to 6 months, 38% up to 12 months and 19% for more than a year. The only risk factor associated with the hazard of death among the factors studied was the performance status of the patients. Patients with PS = 0 presented a median survival time of 13 months and those with PS = 1, it was only 9 months. Non-haematological and haematological toxic effects were generally mild to moderate and entirely manageable.