José Luís Passos-Coelho

Suboptimal survival of male germ-cell tumors in southern Portugal—a population-based retrospective study for cases diagnosed in 1999 and 2000

BACKGROUND The outcome of germ-cell tumors (GCTs) is a hallmark of good-quality cancer care. In the Eurocare-4 study, the mean 5-year survival for patients diagnosed from 1995 to 1999 was 95.5%. PATIENTS AND METHODS We carried out a population-based retrospective chart review study of male patients diagnosed with GCT in 1999 and 2000 in southern Portugal (2 119 065 males). RESULTS There were 87 GCTs-79 testicular, 2 retroperitoneal, 3 mediastinal, 2 of the central nervous system and 1 of the stomach. For the 81 patients with testicular or retroperitoneal primaries, 35 had stage I, 13 stage II and 30 stage III at presentation (3 unknown). Classification by International Germ Cell Consensus Classification Group criteria, 17 belonged to the poor prognosis group (mediastinal primary 3, liver metastases 11 and very elevated markers 3). With median follow-up of 89 months, the 5-year absolute overall survival was 80% (100% for stage I, 92% for stage II and 53% for stage III disease). CONCLUSIONS While GCT incidence was similar to neighboring Spain, the 5-year overall survival was lower than that of other European countries. This may result from delays in diagnosis, suggested by high proportion of high-stage and large-burden disease, and poor adherence to recommended treatment algorithms.

Does Hypoxic Response Mediate Primary Resistance to Sunitinib in Untreated Locally Advanced Breast Cancer

BACKGROUND The antiangiogenic drug sunitinib has never been evaluated as single agent in untreated breast cancer patients. OBJECTIVE We aimed to characterize the activity of sunitinib, alone and with docetaxel, in untreated locally advanced or operable breast cancer and to uncover the mechanisms of response. METHOD Patients were treated with an upfront window of sunitinib followed by four cycles of sunitinib plus docetaxel. Response, resistance and toxicity were evaluated according to standard clinical parameters, magnetic resonance imaging, positron emission tomography, standard pathology characterization, molecular pathology and gene expression profiling. RESULTS Twelve patients were included. We detected primary resistance to sunitinib in the upfront window in untreated breast cancer, as evidenced by four non-responding patients. At surgery, five patients had viable tumor in the breast and axilla, four had viable tumor cells in the breast alone and three were taken off study and thus not evaluated, due to unacceptable toxicity. Early functional imaging was useful in predicting response. There were no clinical complete responses. Comparison of tumor gene expression profiling data between early responders and non-responders allowed us to identify the up-regulation of VEGF and angiogenic pathways in non-responders. Specifically, in tumors resistant to single-agent sunitinib we detected a transcriptional response to hypoxia characterized by over-expression of several HIF1α target genes. CONCLUSION In this report of single-agent sunitinib treatment in untreated localized breast cancer patients, we found evidence of primary resistance to sunitinib, likely mediated by up-regulation of hypoxia responsive genes.

Adjuvant chemotherapy with TAC (docetaxel, doxorubicin, and cyclophosphamide) in patients with breast cancer--incidence of neutropenic fever outside clinical trials.

To the Editor: In a phase III trial in node-positive breast cancer, adjuvant chemotherapy with TAC improved diseasefree and overall survival as compared to FAC (5FU, doxorubicin and cyclophosphamide) but with a high incidence of neutropenic fever (NF, 24.7% versus 2.5% of patients) (1). A subsequent trial showed that primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) reduces the incidence of NF with TAC from 24% to 6.5% of patients (2) but there are little data outside the clinical trials setting. Our aim was to assess the hematologic toxicity of TAC chemotherapy with primary prophylaxis with filgrastim, in patients treated in our referral cancer centre outside clinical trials. All consecutive women treated with adjuvant TAC chemotherapy for node-positive breast carcinoma at our Institution between October 2004 and April 2007 were included. Patients were identified through hospital pharmacy and day-hospital records. Clinical charts and pharmacy dispensing records were reviewed for collection of patient and disease characteristics, treatment administration, toxicity, and filgrastim prophylaxis administration. All patients had a blood cell count before day one of each cycle. No routine cell blood counts were done in between, unless determined by clinical events that led to nonprogrammed hospital visits. NF was defined as axillary temperature above 38 C associated with an absolute neutrophil count (ANC) below 500 ⁄lL, regardless of the need for hospital admission. Descriptive statistics are described as median and ranges. Two-sided 95% confidence intervals (CI) for sample proportions were estimated. This retrospective study included 147 female patients (median age 52 years, range 27–70 48% premenopausal) who had completed treatment at the time of analysis. The majority had T1 (40%) and T2 (56%) tumors; all but one had at least one positive axillary lymph node on pathologic examination (55% one to three, 29% four to nine and 16% ten or more positive nodes); 76% tumors were hormone-receptor positive; 29 tumors were HER-2 ⁄ neu positive and 108 were negative (10 undetermined ⁄ unknown). All patients had undergone primary surgery – breastconserving surgery in 57% and modified radical mastectomy in 43%. All patients received TAC as described by Martin et al. (1) but no prophylactic antimicrobials. Of the 147 patients, 134 received all six scheduled cycles while 12 received less due to prior neutropenic fever or infection (six), neurotoxicity (one), docetaxelhypersensitivity (four) and neutropenia without fever or infection (one); one patient received seven cycles of TAC. Overall, 840 cycles of TAC were administered, (median 6 per patient, range 1–7). There were 31 treatment delays and two dose reductions (Table 1). All patients received primary prophylaxis with filgrastim. Two patients switched to pegfilgrastim (Neulasta; Amgen, Thousand Oaks, CA) on the first and fifth cycles of chemotherapy, respectively. One hundred and thirty-one (89%) started filgrastim prophylaxis between cycle day 2 and 4 and 16 (11%) between days 5 and 9. Thirty patients (20%) received filgrastim for less than 7 days in at least one cycle. The duration of filgrastim administration was less than 7 days in 104 (12%) cycles and 7 days or more in 729 (87%) cycles; pegfilgrastim was given in seven cycles (1%). In some patients filgrastim treatment was continued beyond 7 days due to the development of NF, persistence of neutropenia or NF in a prior cycle. There were 27 NF episodes (3.2% of cycles; CI 2.2–4.7%). Twenty patients had one single episode, Address correspondence and reprint requests to: JL Passos-Coelho, MD, PhD, IPOLFG, Rua Professor Lima Bastos, 1099-023 Lisboa, Portugal, or e-mail: passoscoelho@sapo.pt.

Use of chemotherapy in the last three months of life: A retrospective single centre analysis

8073 Background: There is concern that terminally ill cancer patients (pts) are overtreated with chemotherapy (CT), even when such treatment is unlikely to palliate symptoms. The study objective wa...