Background
Although the optimal management of women with FIGO stages I and II epithelial ovarian cancer (EOC) is still controversial, platinum-based adjuvant chemotherapy (CT) is the mainstay of ...treatment. Suboptimal survival results have led to major efforts to identify prognostic factors, improve surgical staging and develop adjuvant therapies to improve patients’ outcomes.
Patients and methods
We evaluate in a retrospective study clinical efficacy and the toxicity profile of a platinumbased adjuvant CT in FIGO stages I and II EOC treated at our institution from March 1984 to December 2006. Grade I FIGO stages IA-IB were excluded from the analysis. In the first period (1984–1997), patients received a platinumbased regimen without taxanes. In the second period from 1997 onwards, patients were treated with carboplatin and paclitaxel. Four to six cycles of adjuvant CT were administered. Potential predictive factors of efficacy and the role of paclitaxel addition were also analysed.
Results
One hundred and fifty-eight patients (60 treated with paclitaxel) met inclusion criteria and were evaluable. Median age at diagnosis was 53.7 years (range 19–81) and most patients had an Eastern Cooperative Oncology Group performance status score (ECOG) of 0–1 (91.8%); 82.9% patients had pathological stage I and 17.1% pathological stage II. With a median follow up of 8.34 years (range 4.4–11.6), 103 patients (74.1%) were free of disease and 110 of them were alive (79.1%). Median relapse-free survival (RFS) and median overall survival (OS) had not been reached at the time of the analysis. No survival difference was found between paclitaxel and carboplatin combination or non-paclitaxel-containing regimens. Statistically significant prognostic factors for better RFS in the multivariate analysis were: ECOG 0 (
p
=0.023; HR 0.32; 95% CI 0.17–0.57); FIGO I stage (
p
<0.001; HR 0.30; 95% CI 0.15–0.58); I–II histological grade (
p
=0.005; HR 0.38; 95% CI 0.19–0.75); mucinous histology (
p
=0.013; HR 0.28; 95% CI 0.13–0.53); non-surgical adherences (
p
<0.002, HR 0.32; 95% CI 0.15–0.54); paracolic gutters inspection (
p
=0.033; HR 0.50; 95% CI 0.26–0.95) and liver surface biopsies (
p
=0.048; HR 0.64; 95% CI 0.41–0.98). Toxicity was generally mild and non-haematologic events were the most commonly found (62.9% of the total). The most frequent haematologic toxicities were neutropenia (41.7% in all grades, 9.5% grade 3–4) and anaemia (29.1% in all grades, 3.2% grade 3–4).
Conclusions
The long-term outcome of this series is comparable to the published evidence and reflects the limited activity of platinum-based CT in the adjuvant setting. The potential survival advantage of the addition of paclitaxel to carboplatin cannot be definitively answered due to the small number of patients, the limited follow-up and the retrospective nature of the study. More effective and specific treatments are clearly required, in particular for those patients with stage II and undifferentiated tumours. Quality of surgery entails prognostic value.
To determine the activity of successive trastuzumab-containing regimens in HER2-overexpressing metastatic breast cancer (MBC) as well as the response rate (RR), time to progression (TTP), and ...predictive factors for response.
We performed a descriptive retrospective study of trastuzumab activity in patients with HER2-overexpressing MBC treated at our hospital from October 1999 to October 2003.
Fifty-eight patients were evaluated, in whom an overall RR (complete response plus partial response) of 39.7% was obtained for first-time administration of trastuzumab; stable disease (SD) was seen in 29.3%, and the clinical benefit rate was 69%. Median TTP was 6 months (range, 1 months to > 39 months). A total of 31 patients (53.4%) received a second trastuzumab-containing regimen, with an RR of 25.8%; SD was seen in 12.9%, and the clinical benefit rate was 38.7%. Median TTP was 3 months (range, 1 months to > 22 months). A total of 8 patients (14.3%) received a third trastuzumab-containing regimen. The RR for the third trastuzumab regimen was 12.5%; SD was seen in 12.5%, and the clinical benefit rate was 25%. Median TTP was 2 months (range, 1 months to > 12 months). A total of 4 patients (7.1%) received a fourth trastuzumab-containing regimen, with an RR of zero and SD in 25%. Predictive factors for response were disease in soft tissue or bone (
P = 0.03; odds ratio OR, 3.25; 95% confidence interval CI, 1.08–9.8) and metastases at > 2 sites (
P = 0.03; OR, 6.2; 95% CI, 1.25–30.9). We observed a better RR in the second trastuzumab-containing regimen when the patient responded to the first regimen (
P = 0.03; OR, 13.2; 95% CI, 1.36–126).
Trastuzumab-containing regimens beyond disease progression in MBC show activity even in heavily pretreated patients. The activity noted does not allow us to ascertain the independent contribution of trastuzumab in this setting. There were more responses in patients with few metastases in the soft tissues or bone. Patients who have shown a previous response to trastuzumab can show a response to a second trastuzumab-containing regimen.
Material and methods
A prospective study was conducted to determine the value of changes in circulating tumour cell (CTC) levels prior to and after the first cycle of neoadjuvant treatment in early ...prediction of pathologic response in locally advanced breast cancer (LABC). Two blood samples were obtained from 72 eligible LABC patients to isolate and enumerate CTCs before neoadjuvant chemotherapy started on day 1, and on day 21, immediately before second cycle administration.
Results
Sixty patients (83.3%) had <1 CTC in the first sample and response rates in this cohort were pathologic complete response (PCR) in 2 patients (5%), partial response (PR) in 35 (87.5%), stable disease (SD) in 2 (5%) and progressive disease (PD) in 1 (2.5%). Twelve patients (16.7%) had >2 CTCs in the first sample; these patients were more likely to have triple negative tumours. All 12 had fewer CTCs in the second sample. Response rates in this second cohort of 12 patients were PCR in 4 (34%), PR in 6 (50%), SD in 1 (8%) and PD in 1 (8%). PCR rate was markedly better in this second cohort (
p
<0.0042; OR 14.5, 95% CI 2.3–92).
Discussion
This study suggests that the presence of CTCs prior to neoadjuvant therapy might be a predictor of response to this therapy.
CNS metastases mean a great challenge. It has been suggested that the brain metastases incidence could be high in metastasic breast cancer patients receiving trastuzumab based-therapies.
We performed ...a descriptive analysis of our experience in this setting. 86 patients met the criteria (From Oct/99 to Oct/03).
CNS progression occurred in 17 patients (19.5%). Mean age of CNS progression disease patients was 45.4 years while mean age for all the patients was 50.5 years. Response rate for the entire group of patients was: OR 39.7%; CB (OR + SD) 69%. Response rate to trastuzumab based-therapy was OR 82.4% and CB 88.2 at the time of CNS progression. Median time from the start of trastuzumab therapy up to the CNS progression was 10 months. OS was 23.4 weeks.
The incidence of CNS involvement is high in young metastasic breast cancer women responding to trastuzumab-based therapies. This may lead to prophylactic cranial irradiation strategies or to the early detection in asymptomatic patients to improve surgery or radiosurgery results in these patients.
Survival results of stage II colorectal cancer patients have led to major efforts to identify the subset of patients at risk for disease relapse and adjuvant therapies benefit. Immunohistochemistry ...is being explored to detect undetectable microscopic lymph node micrometastases.
A retrospective analysis of a 105 consecutive stage II colorectal cancer patients was performed. Two four-micres sections were obtained from each lymph node. These slides were stained with AE1-AE3 monoclonal antibodies against cytoskeleton using DAKO EnVision visualization system. Micrometastases were identified either as isolated cells or as well-defined glandular cell clusters with cytoplasm but not the nucleus stained with cytoskeleton antibodies.
665 lymph nodes isolated from 105 patients were analyzed. Lymph nodes micrometastases were assessed in 26 out of the 105 patients. 42 (6.3%) out of 665 lymph nodes were infiltrated. Most of these metastases consisted of isolated cell cluster localized in marginal and interfollicular sinus of lymph nodes. The relapse rate was 23.1% among the patients with immunohistochemical detected lymph node micrometastes and 20.3% for the patients without lymph node involvement. This result lacked statistical significance (p = 0.759).
AE1/AE3 lymph node immunohistochemical staining in stage II colorectal cancer is an interesting biological phenomenon but it fails to identify patients at higher risk of relapse who deserve a more aggressive adjuvant attitude.
The relationship between breast cancer and circadian rhythm variation has been extensively studied. Increased breast tumorigenesis has been reported in melatonin-suppressed experimental models and in ...observational studies.
Circulating Tumor Cells (CTC) circadian- rhythm may optimize the timing of therapies. This is a prospective experimental study to ascertain the day-time and night-time CTC levels in hospitalized metastasic breast cancer (MBC) patients.
CTC are isolated and enumerated from a 08:00 AM and 08:00 PM blood collections. 23 MBC and 23 healthy volunteers entered the study. 69 samples were collected (23 samples at 08:00 AM and 23 samples at 08:00 PM from MBC; 23 samples from healthy volunteers). Results from two patients were rejected due to sample processing errors. No CTC were isolated from healthy-volunteers.
No-differences between daytime and night-time CTC were observed. Therefore, we could not ascertain CTC circadian-rhythm in hospitalized metastasic breast cancer patients.
