Prolonged survival after splenectomy in Wiskott-Aldrich syndrome: a case report.

Wiskott-Aldrich syndrome is a rare X-linked immunodeficiency disorder that is characterized by a variable clinical phenotype. Matched donor bone marrow transplantation is currently the only curative therapeutic option. We present the case of a 24-year-old male who was diagnosed at the age of seven with Wiskott-Aldrich syndrome. He did not respond to intravenous gammaglobulin and he experienced recurrent pulmonary infections despite prophylactic antibiotics. The patient had no matched donor. At the age of nine, he was submitted to splenectomy and his platelet count was normalized. Fifteen years later, the patient remains asymptomatic with a normal platelet count. He is still receiving prophylactic antibiotics and no bleeding episodes or septic complications have been reported. This case demonstrates that splenectomy can represent a safe therapeutic option in selected WAS patients, provided that there is a tight follow-up program, patient education and adherence to guidelines regarding post-splenectomy prophylaxis.

Updates on treatment of gemcitabine-refractory pancreatic adenocarcinoma. Highlights from the "2011 ASCO Annual Meeting". Chicago, IL, USA; June 3-7, 2011.

Gemcitabine monotherapy and gemcitabine-based regimens are the current standard of care for locally advanced or metastatic pancreatic adenocarcinoma. However, there is still great controversy over the role of salvage chemotherapy after failure of gemcitabine. This review is an update on the 2011 American Society of Clinical Oncology (ASCO) Annual Meeting regarding the most important developments in the treatment of refractory pancreatic cancer, as they were reported in Abstracts #e14542 and #e14588.

Hypersensitivity reactions to docetaxel: retrospective evaluation and development of a desensitization protocol.

BACKGROUND: Docetaxel (DT) is an extensively used taxane, frequently associated with hypersensitivity reactions. The aim of this study was to record the epidemiological and clinical features of hypersensitivity to DT in non-small cell lung cancer patients in order to obtain useful information concerning the management of these patients. We also developed a desensitization protocol and evaluated its clinical application. METHODS: We retrospectively reviewed records of 620 non-small cell lung cancer patients treated with DT-containing regimens in the adjuvant, first-, second- or next-line setting. Data from 102 patients who had exhibited hypersensitivity reactions were analyzed according to the Common Toxicity Criteria for Adverse Events version 3.0. Five patients were chosen for the desensitization protocol. We applied the standard protocol for parenteral desensitization to ß-lactam antibiotics, and DT treatment was carried out with a series of 10-fold dilutions in sufficient volume to administer the total dose. RESULTS: One hundred and two patients (16.5%) were recorded as having hypersensitivity to DT. Reactions were observed after approximately 2.5 ± 1.0 cycles. Only 14 patients (14/620, 2%) developed grade 3-4 hypersensitivity. Reactions were more likely in patients during second- or third-line chemotherapy, but no other correlation (age, gender, atopic status) was observed. Five patients completed a parenteral desensitization protocol and continued their treatment uneventfully. CONCLUSIONS: Hypersensitivity reactions to DT respond quickly to discontinuation along with appropriate supportive care. Premedication and increased infusion time may allow readministration. The desensitization protocol that we developed provides a reliable alternative to permanent discontinuation of DT.

Treatment for refractory pancreatic cancer. Highlights from the "2011 ASCO Gastrointestinal Cancers Symposium". San Francisco, CA, USA. January 20-22, 2011.

While gemcitabine-based regimens are currently accepted as the standard first-line treatment of patients with locally advanced or metastatic pancreatic adenocarcinoma, there is no consensus regarding treatment in the second-line setting. This review is an update from the 2011 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium regarding recent developments in the treatment of refractory pancreatic cancer, as these were presented in Abstracts #237 and #272 of the meeting.

Phase II study of gemcitabine plus docetaxel as second-line treatment in malignant pleural mesothelioma: a single institution study.

OBJECTIVE: The combinations of cisplatin-pemetrexed and cisplatin-gemcitabine are considered the standard systemic therapy for malignant pleural mesothelioma (MPM), which is a rapidly progressive tumor. The purpose of the present study is to evaluate the efficacy, safety, and clinical benefit of the gemcitabine plus docetaxel regimen in the second-line treatment of this disease. PATIENTS AND METHODS: A total of 37 patients with MPM were treated with the combination of docetaxel (80 mg/m) and gemcitabine (1000 mg/m) on day 1 and 14 of a 28-day cycle. The regimen was repeated for a maximum of 6 cycles or until disease progression or unacceptable toxicity. RESULTS: There was partial response of the disease in 7 patients (18.9%), whereas it remained stable in 23 patients (62.2%) and progressed in 7 patients (18.9%). The median time to disease progression was 7 months (range: 5.8-8.2 months) with a mean survival of 16.2 months (range: 13-19.3 months). CONCLUSION: The biweekly administration of docetaxel and gemcitabine, along with granulocyte colony-stimulating factor support, constitutes a safe, tolerable, and convenient regimen for the treatment of MPM, suggesting that this combination may be a viable option, especially in previously treated patients.

Hypersensitivity reactions associated with platinum antineoplastic agents: a systematic review.

Platinum-containing chemotherapy agents (cisplatin, carboplatin, oxaliplatin) have been approved in the first-line setting of numerous malignancies, such as ovarian, bladder, head and neck, colorectal, and lung cancer. Their extensive use over the last decade has led to a significant increase in the incidence of hypersensitivity reactions, which are defined as unforeseen reactions whose signs and symptoms cannot be explained by the known toxicity of these drugs. Skin rash, flushing, abdominal cramping, itchy palms, and back pain are common symptoms. Cardiovascular and respiratory complications can prove fatal. Multiple pathogenetic mechanisms have been suggested. Hypersensitivity usually appears after multiple infusions, suggesting type I allergic reactions; however, other types of hypersensitivity also seem to be implicated. Several management options are available to treating physicians: discontinuation of chemotherapy, premedication, prolonging of infusion duration, desensitization protocols, and replacement with a different platinum compound after performing skin tests that rule out cross-reactions among platinum agents.

Role and cost effectiveness of PET/CT in management of patients with cancer.

PET/CT is a relatively new imaging technology, whose undoubted advantages are valuable in clinical oncology as well as in all fields of diagnosis, staging, and treatment. The hardware combination of anatomy and function has been the true evolution in imaging. PET using 18F-fluorodeoxyglucose (FDG) is increasingly used for the staging of solid malignancies, including colon, lung, etc., but anatomic information is limited. Integrated PET/CT enables optimal anatomic delineation of PET findings and identification of FDG-negative lesions on computed tomography (CT) images and might improve preoperative staging. However, controversy still exists in relation to the application of PET/CT in clinical practice, mainly because of its high cost. It is evident that apart from additional costs, potential savings also are associated with PET/CT as a result of avoiding additional imaging examinations or invasive procedures and by helping clinicians make the optimum treatment decisions. The authors review the literature on the role of PET/CT in management of various tumors and discuss the medicoeconomic usefulness.

Acute hypersensitivity reactions to chemotherapy agents: an overview.

Hypersensitivity reactions to chemotherapy agents are defined as unexpected reactions with signs and symptoms not consistent with known toxicity of these drugs. These reactions range from mild to life-threatening and are difficult to predict. Symptoms include flushing, nausea, difficulty breathing, back pain, hypotension and tachycardia. Hypersensitivity is commonly encountered owing to the increasing use of chemotherapy drugs in clinical practice. The pathogenetic mechanisms are not fully understood but they seem to vary between agents. Reactions to taxanes usually occur during the first few minutes of the first or second infusion, whereas acute reactions to platinum agents usually occur after multiple cycles of therapy. Basic principles that allow management and possible completion of the regimen should be followed. Certain protocols aim to prevent acute reactions by slowing the infusion rate and by administering steroid and histamine receptor antagonists. Skin testing and desensitization protocols have also been successfully used in case of hypersensitivity to various chemotherapy drugs. Knowledge of all available management options assists physicians in making the most appropriate decision regarding further treatment.

Triplet combination of carboplatin, irinotecan, and etoposide in the first-line treatment of extensive small-cell lung cancer: a single-institution phase II study.

Small-cell lung cancer is a rapidly progressive tumor and median survival is less than 10 months in patients with extensive stage of the disease. This study aims to evaluate the efficacy and tolerability of the carboplatin, etoposide, and irinotecan triplet as a first-line treatment in extensive small-cell lung cancer. Chemonaive patients with documented diagnosis of extensive small-cell lung cancer, performance status 0-2, and adequate organ function were eligible. Patients received triweekly carboplatin area under the curve 5 on day 1, irinotecan 150 mg/m on day 2, and etoposide 75 mg/m on days 1, 2, and 3 for up to six cycles. A total of 54 patients were enrolled. Forty-seven of 54 patients (87%) had a performance status of 0-1. The response rate was 75% and complete response was achieved in 10 of 54 patients (18%). The median time to progression was estimated at 8 months (95% confidence interval: 6.6-8.9) and median overall survival at 12 months (95% confidence interval: 10.3-13.9). Patients with one site of metastases had prolonged survival as compared with those with two or more sites. Normalization of lactate dehydrogenase values after treatment was not correlated to survival. Grade 3-4 neutropenia occurred in nine patients (16.7%) and grade 3 fetal thrombocytopenia in one patient (1.9%). Two toxic deaths (3.7%) were reported. The carboplatin, irinotecan, and etoposide triplet is a very effective and well-tolerated combination for the poor prognosis group of extensive-stage small-cell lung cancer patients.

Carboplatin plus pemetrexed as first-line treatment of patients with malignant pleural mesothelioma: a phase II study.

INTRODUCTION: Malignant pleural mesothelioma (MPM) is a rapidly progressive tumor that is increasing in frequency worldwide. Treatment options are limited, and response to chemotherapy is poor. The aim of this phase II study was to evaluate the activity of the carboplatin/pemetrexed combination as first-line chemotherapy in patients with unresectable MPM. PATIENTS AND METHODS: Chemotherapy-naive patients with histologically confirmed MPM and an Eastern Cooperative Oncology Group performance status of 0-2 were enrolled. Treatment consisted of pemetrexed 500 mg/m2 and carboplatin area under the concentration-time curve of 5 mg/mL/min, both administered on day 1 of a 21-day cycle. The treatment continued until 6 cycles were completed or until unacceptable toxicity or disease progression were observed. RESULTS: A total of 62 patients were enrolled. Of these patients, 18 (29%) had a confirmed partial response, whereas the disease remained stable in 34 patients (54.9%) and progressed in 10 patients (16.1%). The median overall survival (OS) was estimated at 14 months (95% CI, 11.8-16.2 months), and the median time to progression was 7 months (95% CI, 5.8-8.2 months). The difference in median OS between the epithelial histologic subtype (16 months) and the sarcomatoid subtype (11 months) was statistically significant. CONCLUSION: This study confirmed the activity of the carboplatin/ pemetrexed combination in the first-line treatment of patients with MPM. It is a viable option, especially in cases in which side effects are generally anticipated.

Effects of taxane-based chemotherapy on inhibin B and gonadotropins as biomarkers of spermatogenesis.

OBJECTIVE: To assess the effects of taxane-based chemotherapy on the male reproductive axis, and, therefore, its impact on spermatogenesis and fertility. DESIGN: Controlled clinical study. SETTING: Patients with cancer in an academic research environment. PATIENT(S): Forty male patients of reproductive age with cancer with solid tumor at diagnosis, who had been scheduled to receive taxane-based chemotherapy. INTERVENTION(S): The patients were given treatment with docetaxel or paclitaxel combined with gemcitabine or carboplatin. Blood sampling and testicular ultrasonography were performed before and after completion of chemotherapy. MAIN OUTCOME MEASURE(S): In all patients, serum levels of inhibin B, FSH, and LH were measured, and, in half of the patients, bilateral testicular volume was also measured. RESULT(S): There was a statistically significant decrease in serum inhibin B and increase in serum FSH in all patients after the completion of the taxane-based chemotherapy. The median LH levels did not exhibit a statistically significant increase after the last cycle. Bilateral testicular volume exhibited a statistically significant decrease in 19 out of 20 patients (95%) after completion of chemotherapy. CONCLUSION(S): Taxane-based chemotherapy induces the reduction of inhibin B and the reciprocal elevation of FSH, which are associated with significant gonadal damage in the early stages after completion of chemotherapy.

CoFactor: Folate Requirement for Optimization of 5-Fluouracil Activity in Anticancer Chemotherapy.

Intracellular reduced folate exists as a "pool" of more than 6 interconvertable forms. One of these forms, 5,10 methylenetetrahydrofolic acid (CH(2)THF), is the key one-carbon donor and reduced folate substrate for thymidylate synthase (TS). This pathway has been an important target for chemotherapy as it provides one of the necessary nucleotide substrates for DNA synthesis. The fluoropyrimidine 5-fluorouracil (5-FU) exerts its main cytotoxic activity through TS inhibition. Leucovorin (5-formyltetrahydrofolate; LV) has been used to increase the intracellular reduced folate pools and enhance TS inhibition. However, it must be metabolized within the cell through multiple intracellular enzymatic steps to form CH2THF. CoFactor (USAN fotrexorin calcium, (dl)-5,10,-methylenepteroyl-monoglutamate calcium salt) is a reduced folate that potentiates 5-FU cytotoxicity. According to early clinical trials, when 5-FU is modulated by CoFactor instead of LV, there is greater anti-tumor activity and less toxicity. This review presents the emerging role of CoFactor in colorectal and nongastrointestinal malignancies.

Bevacizumab may be active in myelofibrosis.

A case of a 69-year-old woman with myelofibrosis presenting with non-small cell lung cancer was reported at Sotiria General Hospital in Athens. She was administered bevacizumab infusions biweekly and a great decrease in the number of her white blood cells was observed. Such low levels of white blood cells had never been reached in the past, when she was receiving hydroxyurea.

Administration of cisplatin in three patients with carboplatin hypersensitivity: is skin testing useful?

Carboplatin is a chemotherapeutic agent approved in the first-line setting of numerous malignancies. Hypersensitivity to carboplatin has been reported in up to 44% of patients receiving this antineoplastic agent, usually occurring after several courses of treatment. The aim of this study was to determine the usefulness of skin tests in ruling out cross-reaction to cisplatin to continue platinum-based chemotherapy in patients who are responsive to these agents. Prick tests and intradermal tests with a series of dilutions of carboplatin and cisplatin were performed on three patients who had exhibited medium and severe hypersensitivity reactions to carboplatin. Prick tests were negative in both the antineoplastic agents. Intradermal tests with carboplatin were positive in all three patients and negative with cisplatin. In all patients, the administration of cisplatin instead of carboplatin was well tolerated without the need of premedication. In conclusion, intradermal skin tests can be a useful tool for detecting a potential cross-reaction between platinum salts. It allows safe administration of a different platinum agent in patients who seem to benefit from platinum-based therapy. Discontinuation of chemotherapy, desensitization protocols and steroid premedication can be avoided.

Cell adhesion molecules: role and clinical significance in cancer.

There is a growing body of evidence suggesting that alterations in the adhesion properties of neoplastic cells endow them with an invasive and migratory phenotype. Indeed, changes in the expression or function of cell adhesion molecules have been implicated in all steps of tumor progression, including detachment of tumor cells from the primary site, intravasation into the blood stream, extravasation into distant target organs, and formation of the secondary lesions. This review presents recent data regarding the role of cell adhesion molecules in tumor development and progress with concern to their clinical exploitation as potential biomarkers in neoplastic diseases.

The role of angiogenesis in solid tumours: an overview.

Angiogenesis is the physiological process of the formation of new blood vessels from pre-existing ones. Multiple molecules regulate angiogenesis, such as the vascular endothelial growth factor, angiopoietins, the fibroblast growth factor, the platelet-derived growth factor and the transforming growth factor-beta. Angiogenesis plays an important role in the growth, progression and metastasis of a tumour. Inhibiting the angiogenic process or targeting existing tumour vessels can be used for treatment of tumours as an alternative or in parallel with conventional chemotherapy. Many anti-angiogenic factors are under investigation and some are already being used in clinical practice with various results.

Docetaxel plus gemcitabine as first-line treatment in malignant pleural mesothelioma: a single institution phase II study.

BACKGROUND: The cisplatin-pemetrexed and cisplatin-gemcitabine combinations are considered the standard treatment for malignant pleural mesothelioma. The purpose of this study was to examine the efficacy of gemcitabine plus docetaxel in the first-line setting, as this combination has not been investigated in mesothelioma before. PATIENTS AND METHODS: Twenty-five consecutive patients with malignant pleural mesothelioma were enrolled. They received 80 mg/m(2) of docetaxel and 1,000 mg/m(2) of gemcitabine on days 1 and 14 of a 28-day cycle. The treatment was scheduled for a maximum of 6 cycles or until disease progression or unacceptable toxicity. RESULTS: A total of 7 out of our 25 patients (28%) responded to treatment. In 14 patients (56%), the disease remained stable, while in 4 (16%) it progressed. The median time to progression was 7 months (range: 5.4-8.6 months) and the median overall survival was 15 months (range: 12.4-17.5 months). CONCLUSION: The administration of gemcitabine and doctaxel appears to be promising first-line therapy for patients with mesothelioma, as it is well tolerated and appears to improve survival.

Thrombotic microangiopathy associated with gemcitabine: rare but real.

Gemcitabine-associated thrombotic thrombocytopenic purpura is a rare complication of gemcitabine treatment with an incidence ranging from 0.015 to 1.4%. Clinically, this disease manifests as haemolytic anaemia, thrombocytopenia and renal insufficiency; hypertension and neurological and pulmonary symptoms are also known complications. The risk of thrombotic thrombocytopenic purpura increases as the cumulative dose of gemcitabine approaches 20,000 mg/m(2). The pathophysiology of this disease entity is unknown although several theories, involving both immune and non-immune mechanisms, have been proposed. The most effective treatment is discontinuation of gemcitabine, the provision of antihypertensive medications as needed, and consideration of plasmapheresis or use of immunoadsorption column in severe cases.

Hypersensitivity reactions to antineoplastic agents: an overview.

Hypersensitivity reactions to antineoplastic agents are defined as unexpected reactions with signs and symptoms inconsistent with known toxicity of antineoplastic drugs. These reactions are uncommon and usually associated with certain antineoplastic categories, such as taxanes, platinum-containing compounds, epipodofyllotoxins, asparaginase, procarbazine and, more rarely, with doxorubicin and 6-mercaptopurine. The mechanisms that are responsible for hypersensitivity reactions are unclear and vary between agents. Symptoms of these reactions range from mild skin rashes to more severe reactions, such as arthralgia, respiratory arrest or even death in some cases. Once hypersensitivity reactions are observed, basic principles that allow their management and possible continuance and completion of the regimen should be followed.