Anthony Goldberg

Staphylococcus aureus Bacteremia Secondary to Severe Erlotinib Skin Toxicity

Epidermal growth factor receptor (EGFR) inhibitors are associated with unique and dramatic dermatologic side effects. Skin rash is the dose-limiting factor for all EGFR inhibitors and is usually dose related and reversible. Microbiologic stains and cultures from skin rash usually do not show an infectious cause. We report on a patient with known non-small-cell lung cancer who developed Staphylococcus aureus bacteremia secondary to severe erlotinib skin toxicity.

Metformin As an Addition to Conventional Chemotherapy in Breast Cancer

metformin inbreast cancer may be related to activation of adenosine monophosphate‐activated protein kinase, which may ultimately result in a rapid inhibition of cellular protein synthesis and growth of tumor cells. We suggest, however, that additional mechanisms may play a part. It is a well-accepted fact that chronic inflammation is a major contributory factor to cancer development and progression, and elevated levels of various nonspecific markers of inflammation in the serum have been shown to be associated with poor survival in a number of different cancers. Pierce et al 3 have recently assessed the relationship between circulating levels of C-reactive protein and serum amyloid A and breast cancer survival. They showed that raised levels of these inflammatory markers were associated with a significantly reduced overall survival and a trend toward a reduced diseasefreesurvival.Patientswithtype2diabetesmellitustendtohavehigher C-reactive protein concentrations than those without it, suggesting that inflammation may contribute to the higher risk of breast cancer and worse prognosis of malignant disease in these patients. 4 Thereisevidencetosuggestthatmetforminhasapositiveimpact on inflammation and endothelial dysfunction. Metformin was compared with another oral hypoglycaemic agent, repaglinide, in nonobese patients with type 2 diabetes and shown to be more effective in

Long-term response to pegylated liposomal doxorubicin in patients with metastatic soft tissue sarcomas.

Doxorubicin and ifosfamide are currently considered the cornerstones of treatment for advanced soft tissue sarcomas (STSs). Pegylated liposomal doxorubicin (PLD) has been shown to have equivalent activity to doxorubicin and an improved toxicity profile. A review of the medical records of 11 patients with a variety of STSs treated with PLD was performed. The median age of the patients was 54.8 years. Of the 11 patients, seven received no earlier systemic therapy for their sarcoma. The initial dose per course was 40–60 mg/m2 every 4 weeks with dose reduction to 40 mg/m2 in the second or third cycle. A median of 11 cycles was given (range, two to 29 cycles). Treatment was generally well tolerated. We did observe some toxic effects as described earlier with PLD, including mild myelosuppression, skin toxicity and fatigue. No cardiotoxicity was observed. Of the 11 treated patients, six had a partial response, two had a best response of stable disease and three had progressive disease. All six patients with a partial response had an extended time to progression. To date, two patients continue on treatment (15 and seven cycles); one patient has stable disease 60 months after withdrawal of PLD (after eight cycles) and one patient had progression of disease 7 months after the withdrawal of therapy after 20 cycles. Of the two patients with stabilization of their disease, one had progression after 29 months and one continues on treatment for 6 months. PLD is active and safe for long-term treatment of metastatic STSs and may be important in maintaining response.

Monitoring long-term treatment with pegylated liposomal doxorubicin: how important is intensive cardiac follow-up?

Pegylated liposomal doxorubicin (PLD; Doxil or Caelyx) has been shown to be as effective as conventional doxorubicin, and to have a significantly better cardiac safety profile. The aim of this study was to assess the safety of delivering doses exceeding 700 mg/m2 of PLD to patients with solid tumors. A review of the medical records of 149 patients with a variety of solid tumors treated with PLD was performed. The findings in 12 patients who had reached or exceeded cumulative doses of 700 mg/m2 (median=1.071 mg/m2, range 712–1856 mg/m2) were reviewed. Changes in left ventricular ejection fraction (LVEF), and in clinical cardiac status were analyzed. The median age of the patients was 53.9 years and the median follow-up from the start of PLD treatment was 44.6 months. None of the 12 patients had clinical congestive heart failure secondary to cardiomyopathy. Seven of the 12 patients underwent further assessment of LVEF by echocardiography or multiple gated acquisition scan, which revealed a stable or improved ejection fraction.PLD is cardiac safe for long-term treatment of metastatic solid tumors. Its maximal cumulative dose remains undefined. Frequent determinations of LVEF, as routinely done for other anthracyclines, do not appear to have any clinical value in patient follow-up. In metastatic patients with no evidence of cardiac risk factors, it may be sufficient to measure LVEF at baseline.

Indwelling central venous access port insertion during bevacizumab-based therapy.

Indwelling central venous catheters and implantable port systems are widely used in the care of patients with cancer. Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, significantly prolongs survival when added to intravenous 5-fluorouracil-based chemotherapy as first-line treatment for metastatic colorectal cancer. It has also been shown to be of value in a range of other malignant diseases. Some elements of the toxicity profile of bevacizumab, however, such as bleeding and impaired wound healing, could interfere with surgical procedures involved in the treatment of the diseases. The aim of this study was to evaluate the possible effect of bevacizumab in increasing the morbidity associated with an indwelling central venous access port in patients currently receiving the drug, or those who had received it in the preoperative run-up to surgery. An analysis of the medical records of 57 patients with a variety of cancers, who had received an indwelling central venous access port, either during the course of treatment with bevacizumab or in the 4-week period before the commencement of therapy was carried out, with particular emphasis on periprocedural complications. Eight of the patients also had diabetes mellitus. There were no instances of delay in wound healing, abnormal bleeding, or wound infection in any of the patients and no episodes of skin ulceration during bevacizumab treatment. Although this is a relatively small study, and no definitive conclusions can be drawn at this stage, our data suggest that an indwelling central venous access port insertion may be carried out shortly before or during bevacizumab treatment without increasing periprocedural morbidity.

Combination therapy with oxaliplatin and 5-fluorouracil in a patient with severe hepatic dysfunction associated with metastatic adenocarcinoma of the large bowel

Oxaliplatin has been shown to be valuable in the treatment of patients with colorectal cancer. Many of these patients will develop liver metastases during the course of their disease, with, in some cases, severe hepatic dysfunction. Although single agent oxaliplatin can be administered safely in patients with severely compromised liver function (as it is not metabolized by the liver), little is known of its safety in these patients when administered in the preferred combination with 5-fluorouracil (which is metabolized by the liver) and leucovorin (FOLFOX protocol). We report on a very sick patient with major liver dysfunction, a bilirubin of 11.2 mg/dl (190 micromol/dl) and an open abdominal wound, for whom palliative hospice care alone was originally proposed, who responded dramatically to the combination. His bilirubin fell to 0.6 mg/dl (10.2 micromol/dl) and his liver function tests returned to near normal levels. The combination was well tolerated and clinical improvement continued for more than 11 months before disease progression was observed.

Long-Term Survival in a Patient with Non-Small Cell Lung Cancer Presenting as Small Intestinal Obstruction

Background: Despite the early and widespread dissemination of nonsmall cell lung cancer, clinically significant metastases in the small bowel are rare, and when they do occur, the patient is almost always in the terminal stages of the disease. Case Report: We report on a patient who presented initially with small bowel obstruction resulting from metastatic spread of a squamous cell carcinoma of the lung. Following surgical removal of the affected bowel, the patient underwent radiofrequency ablation of the lung tumor and subsequent lower lobe resection. The patient continues to be free of disease 2 years from the initial diagnosis. Conclusions: This report highlights the need for a timely diagnosis of an acute surgical abdomen and for the inclusion of small intestinal metastases in the differential diagnosis of the acute abdomen in a patient with a lung cancer. Resection of the obstructing tumor and postoperative systemic therapy should be considered. In cases of isolated metastases, resection of the primary lung tumor is indicated.

Lymph Node Collision Tumor of Non-Small Cell Lung Carcinoma and Chronic Lymphocytic Leukemia

Physical examination on presentation revealed a tender right supraclavicular mass measuring 3 × 4 cm. There was, in addition, mild, nontender enlargement of the axillary lymph nodes bilaterally, but no hepatoor splenomegaly. The peripheral blood showed a white cell count of 47.7 × 10 (reference range: 5–11 × 10); a hemoglobin of 13.2 g/dl (reference range: 14.0–18.0 g/dl), and a platelet count of 353 × 10/l (reference range: 150,000–450,000 platelets per ml). In addition, immunoglobulin levels were normal and b2-microglobulin levels were moderately elevated with 3,712 UG/l ( reference range: 550–2,300 UG/l). A computed tomography (CT) scan of the chest disclosed a 3-cm mass in the right lower lobe, increased interstitial and septal thickening in the right lung, and axillary, mediastinal and supraclavicular lymphadenopathy. Transthoracic biopsy identified the right lower lobe mass as a primary lung adenocarcinoma. Immunohistologic staining of the specimen was positive for cytokeratin 7 and thyroid transcription factor 1, and negative for cytokeratin 20. A right supraclavicular lymph node trucut biopsy was performed. Pathological examination showed destruction of the normal nodal architecture by a lymphoproliferative disorder composed of small cells (fig. 1 A) which on immunohistochemistry were CD20-positive (fig. 1 C) and cytokeratin 7-negative (fig. 1 D), compatible with small lymphocytic lymphoma (SLL). There was a second population of malignant cells in many of the same high power fields within the biopsy specimen (fig. 1 B), with opposite cytologic and architectural characteristics to the CLL component. These were NSCLC carcinoma cells which on immunohistochemistry were positive for cytokeratin 7 (fig. 1 D) and negative for CD20 (fig. 1 C). Cytogenetic studies were neither performed at primary diagnosis of CLL nor at the time of diagnosis of NSCLC. Furthermore, the epidermal growth factor receptor (EGFR) mutational status was not checked as gefitinib was not yet available for first line treatment of NSCLC at that time. In view of the fact that the patient had metastatic disease, treatment with cisplatin, pemetrexed, and bevacizumab was commenced. The patient tolerated the treatment well, and experiencing only modest fatigue and nausea. During the treatment, the peripheral blood showed a white cell count reduction to 16.5 × 10; neutrophils 2.5 × 10 (reference range: 1.8–6.6 × 10); lymphocytes 13.02 × 10 (reference range: 1.1–3.5 × 10); hemoglobin of 10.6 g/dl, and a platelet count of 151 × 10/l. The patient’s dyspnea and cough improved. A follow-up CT scan showed significant improvement with decreased lymphangitic spread and reduced size of the right lower lobe mass and right supraclavicular lymph nodes. Further scans taken 4, 6 and 8 months later showed stabilization of the partial response. After 6 cycles and 9 cycles respectively, cisplatin and pemetrexed were discontinued, and the patient continued with bevacizumab only.

Reinduction of hormone sensitivity to goserelin following chemotherapy with vinorelbine in castration-resistant prostate cancer.

Primary androgen ablation leads to symptomatic improvement and a reduction in prostate-specific antigen (PSA) serum levels in patients with advanced prostate cancer, but all patients eventually become refractory to hormone therapy with progression of the disease and a life expectancy of about a year. We describe a patient who developed castration resistance, was treated with vinorelbine, and continues to be progression free on therapy with luteinizing hormone releasing hormone agonists alone, more than 2.5 years following cessation of treatment with vinorelbine.