Underuse of Anthracyclines in Women with HER‐2+ Advanced Breast Cancer

Anthracyclines are among the most active drugs in breast cancer. Because of excessive cardiotoxicity, their use in combination with trastuzumab has been discouraged in patients with human epidermal growth factor receptor (HER)‐2⁺ metastatic breast cancer. We sought to describe how this treatment paradigm influenced the use of anthracyclines in this patient setting. We analyzed a multi‐institutional database containing the treatment history of 450 patients who received at least one trastuzumab‐based regimen for HER‐2⁺ metastatic breast cancer. Patients were considered eligible for anthracyclines for metastatic disease if they were never exposed (NE) or had been previously exposed (PE) to an anthracycline in the neoadjuvant or adjuvant setting and had relapsed after 12 months from the last dose. We then assessed the use of anthracycline‐based therapy after failure with the first trastuzumab‐based regimen in eligible patients. Three‐hundred twenty‐one patients were considered eligible for anthracyclines. In total, 190 eligible patients developing disease progression during the initial trastuzumab‐based therapy were analyzed. An anthracycline was administered as first salvage treatment in 14 NE and two PE patients. Another 15 NE and nine PE patients received an anthracycline as a further line of therapy. Of 119 eligible patients who died from breast cancer, only 30 received an anthracycline for metastatic disease. In conclusion, despite the fact that two thirds of the patients receiving trastuzumab‐based therapy for HER‐2 metastatic breast cancer are eligible for anthracyclines, these drugs are infrequently used nowadays to treat trastuzumab‐refractory disease. A role for these compounds should be redefined in this patient subset.     

Phase II study of an all-oral combination of vinorelbine with capecitabine in patients with metastatic breast cancer

Purpose  Combination of intravenous (i.v.) vinorelbine and capecitabine was shown to be feasible and effective in metastatic breast cancer (MBC). In an effort to improve patient convenience and to prolong infusion-free survival, we investigated in first-line treatment a regimen combining oral vinorelbine and capecitabine in a phase II study. Patients and methods  Fifty-two patients (median age, 60 years) with MBC received the combination consisting of oral vinorelbine 60 mg/m² on days 1, 8 and 15 plus capecitabine 1,000 mg/m² bid given from day 1 to day 14 in an open-label, multicentre phase II study [the recommended doses were established in a phase I study (Nolé et al. in Ann Oncol 17:332–339, 2006)]. Cycles were repeated every 3 weeks. Results  Seventy-nine percent of the patients had received prior adjuvant chemotherapy and 81% presented with visceral involvement. The median number of administered cycles per patient was 7 (range 1–18). Twenty-three responses were documented and validated by an independent panel review, yielding response rates of 44.2% (95% CI, 30.5–58.7) in the 52 enrolled patients and 54.8% (95% CI, 38.7–70.2) in the 42 evaluable patients. Median progression-free survival and median overall survival were 8.4 and 25.8 months, respectively. Neutropenia was the main dose-limiting toxicity but complications were uncommon, only one patient having experienced febrile neutropenia. Other frequently reported adverse events included, fatigue, nausea, vomiting, diarrhoea and constipation, stomatitis and hand-foot syndrome, which were rarely severe. Conclusions  This regimen combining oral vinorelbine with capecitabine is effective and manageable in the first-line treatment of MBC. Oral vinorelbine on days 1, 8 and 15 with capecitabine from days 1 to 14 every 3 weeks represents a convenient option which offers an all-oral treatment to the patients and prolongs their infusion-free survival.     

Pitfalls in CT diagnosis of appendicitis: Pictorial essay

Despite the high diagnostic accuracy of CT for appendicitis, numerous pitfalls exist that may result in a misdiagnosis. This pictorial review outlines the potential pitfalls in the CT diagnosis of appendicitis that includes atypical position of the appendix and coexisting pathologies. Various mimickers of appendicitis and clinical dilemmas will be highlighted. Upon completion, the reviewer should have an improved ability to recognise appendicitis mimickers and identify equivocal or atypical findings.     

Marrow harvesting from normal donors

The experience at a single institution in harvesting marrow for allogeneic transplantation on 1,270 occasions from 1,160 normal donors is presented in detail, together with an analysis of all the donor complications. Four donors were less than 2 years old, and the youngest was 6 1/2 months. No special difficulties were encountered with these young donors. Hospitalization time was three days or less for 99% of the procedures. Six donors had life-threatening complications; three of a cardiopulmonary and two of an infectious nature, and one cerebrovascular embolic episode. Significant operative site morbidity, usually transient neuropathies, occurred in ten procedures. Ten percent of the donations were associated with transient postoperative fever of unknown origin. Increasing donor age was associated with a reduction of the cellularity of the marrow harvest. The use of stored autologous blood permitted the avoidance of blood bank transfusion in 81% of males, 69% of females, and 50% of children. It was concluded that the procedure was associated with a very low risk of complication, but that the involvement of normal donors in such an operation justifies stringent monitoring.     

Allogeneic marrow transplantation for refractory anemia: a comparison of two preparative regimens and analysis of prognostic factors

From 1990 to 1993 we performed a prospective study of busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) in 30 patients with refractory anemia (RA) undergoing related (n = 17) or unrelated (n = 13) donor marrow transplantation. Nineteen patients survive disease free (63% 3- year actuarial disease-free survival [DFS]) and no patient relapsed. These results were compared to those of 38 historical controls with RA treated with cyclophosphamide and total body irradiation, of whom 22 are disease-free survivors and 1 relapsed. After correcting for significant variables between the two treatment groups, we found no statistically significant difference in outcome based on preparative regimen. Combining data from these 68 patients plus 2 additional patients with RA treated before 1993 with busulfan and cyclophosphamide, we identified four variables independently associated with improved survival: younger age, shorter disease duration, lower neutrophil count pretransplant, and lower hematocrit pretransplant. We also found that 15 patients 40 to 55 years of age had a 46% 3-year actuarial DFS and 26 patients receiving unrelated or mismatched related donor marrow had a 50% 3-year actuarial DFS. We conclude that there does not appear to be any significant difference in outcome based on preparative regimen in this patient population. In addition, allogeneic bone marrow transplantation may be a reasonable approach to therapy of RA early after diagnosis. However, whether early intervention with transplantation prolongs survival over that expected without transplantation cannot be ascertained with certainty from available data.     

Unrelated donor marrow transplantation in children

Eighty-eight children 0.5 to 17 years of age (median, 9 years of age) received an unrelated donor marrow transplant for treatment of chronic myeloid leukemia (CML; n = 16), acute lymphoblastic leukemia (ALL) in first or second remission (n = 15) or more advanced stage (n = 28), acute myeloid leukemia (AML; n = 13), or other hematologic diseases (n = 16) between June 1985 and April 1993. All patients were conditioned with cyclophosphamide and total body irradiation and received a combination of methotrexate and cyclosporine as graft-versus-host disease (GVHD) prophylaxis. Fourty-six patients received transplants from HLA-identical donors and 42 patients received transplants from donors who were minor-mismatched at one HLA-A or B or D/DRB1 locus. The Kaplan-Meier estimates of disease-free survival and relapse were 75% and 0% for patients with CML, 47% and 20% for ALL in first or second remission, 10% and 60% for ALL in relapse or third remission, 46% and 46% for AML in first remission (n = 1) or more advanced disease (n = 12), and 29% and 69% for other diseases. HLA disparity was not significantly associated with lower disease-free survival, but the results suggest more relapses in HLA-matched recipients and there was significantly more transplant-related mortality in mismatched recipients (51% v 24%, P = .04). Most deaths were due to infections associated with acuteor chronic GVHD and occurred within the first 2 years after transplantation. Granulocyte engraftment occurred in all evaluable patients. Sixty-three percent of HLA-matched and 57% of HLA- mismatched recipients were discharged home disease-free at a median of 98 and 103 days, respectively, after transplantation (P = not significant [NS]). The incidence of grades II-IV acute GVHD was 83% in HLA-matched and 98% in HLA-mismatched recipients (P = .009). The incidence of chronic GVHD was 60% in HLA-matched and 69% in HLA- mismatched recipients (P = NS). One or multiple late adverse events such as cataracts, osteonecrosis of the hip or knee, restrictive or obstructive pulmonary disease, and hypothyroidism have occurred in 11 of 33 (33%) surviving patients. Immunosuppression was discontinued in 58% of surviving patients, including all 12 patients surviving more than 3.2 years, all of whom have a Lansky or Karnofsky score of 100%.(ABSTRACT TRUNCATED AT 400 WORDS)