Second high-dose chemotherapy intensification followed by hematopoietic stem cell transplantation applying a novel high-dose topotecan-based regimen in an adult Wilms' tumor patient: case report.

High-dose chemotherapy and hematopoietic stem cell support remains a valuable treatment option for the rare patient population with relapsed Wilms' tumor. Here we report the case of a 22-year-old male patient treated with two cycles of high-dose chemotherapy at relapse after nephrectomy and adjuvant chemotherapy; the first cycle with melphalan--etoposide--carboplatin and the second with a novel preparative regimen incorporating high-dose topotecan (topotecan--cyclophosphamide--melphalan). A detailed discussion and literature review pertaining to that case is provided.

Double high-dose chemotherapy and stem cell transplantation in adult Wilms' tumor.

High-dose chemotherapy intensification and hematopoietic stem cell support remains a valuable treatment option for the rare patient with relapsed Wilms' tumor. We report a 22-year-old adult male with an initially diagnosed stage II Wilms' tumor, treated by nephrectomy followed by adjuvant chemotherapy. After 1 year, an intra-abdominal relapse was treated with salvage ifosfamide carboplatin etoposide chemotherapy followed by autologous hematopoietic stem cell mobilization. It was intended that he would receive two tandem cycles of high-dose chemotherapy; the first consisting of melphalan etoposide carboplatin; however, the patient did not return to receive the second cycle while in remission, but did return later with grossly relapsed disease. He was then treated with a novel preparative regimen incorporating high-dose topotecan (topotecan, melphalan and cyclophosphamide). This case confirms the feasibility of double high-dose chemotherapy with hematopoietic stem cell support in relapsed Wilms' tumor. A detailed discussion with an extensive review of the literature, regarding studies evaluating the role and indications of high-dose chemotherapy in Wilms' tumor is provided.

Malignant peripheral nerve sheath tumor in neurobifromatosis type-1: two case reports.

INTRODUCTION: Malignant peripheral nerve sheath tumors are rare soft tissue sarcomas. They are considered to carry a poor prognosis with current therapeutic approaches. Successful treatment depends on a multimodal approach. CASE PRESENTATION: The authors report two cases with malignant peripheral nerve sheath tumors arising from pre-existing neurofibromas in the grounds of neurofibromatis-type I. Complete surgical removal of all lesions is considered before and after induction chemotherapy. Correlation of the response to chemotherapy in the context of the immuno-histopathological features of the tumors is also discussed with reference to the existing literature. CONCLUSION: A need for a multidisciplinary approach with chemotherapy, surgery and radiotherapy is anticipated in the management of malignant peripheral nerve sheath tumors as described in these two reported cases. It is felt that further research on the molecular aspects of malignant peripheral nerve sheath tumors and neurofibromatis-type I will optimize treatment strategies in the future.

Cardiotoxicity of fluoropyrimidines in different schedules of administration: a prospective study.

BACKGROUND: Cardiotoxicity associated with 5-Fluorouracil (5FU) administration has been infrequently reported in literature, albeit various series of acute coronary syndromes have recorded a low but definite incidence of the above toxicity. In the present study, patients undergoing 5FU-based and oral capecitabine (Xeloda-based chemotherapy were tested for the potential development of cardiac-related symptoms during their administration. PATIENTS AND METHODS: Six hundred and forty-four patients entered the study. Those experiencing any cardiac-related symptoms during 5FU infusion or oral capecitabine were subjected to ECG and serum cardiac enzymes determination. If cardiotoxicity was confirmed, 5FU infusion or oral capecitabine were interrupted, sublingual nitrates administered and cardiac monitoring initiated, while patients with >two-fold enzyme elevation were followed in a coronary care unit for at least 72 h. Cases with acute myocardial infarction were excluded from further 5FU or oral capecitabine treatment. RESULTS: Overall 26 patients (4.03%) developed symptoms and/or ECG abnormalities due to 5FU and capecitabine. Patients with continuous 5FU infusion presented a higher incidence of cardiotoxicity [14/209; 6.7%, 95% confidence interval (CI) = 3.3-10.1%] than the remaining (7/317; 2.3%, 95% CI = 0.8-3.3%) (P < 0.012). Specifically, an increased incidence of cardiac-related events was encountered in patients with continuous 24-h 5FU + LV infusion for 5 days (12.5%, 95% CI = 2.3-22.7%) rather than in patients with the same schedule without LV (5.3%, 95% CI = 1.95-8.67%) (P < 0.027), as well as in patients with short 5FU + LV administration (2.4%, 95% CI = 0.9-3.9%) (P < 0.019). Overall, 3/54 patients (5.5%, 95% CI = -0.6-11.1%) on oral capecitabine developed cardiac-related events. Seven out of the 20 patients suffered an acute myocardial infarction, 6 developed ischemia only, while 4 more patients had ECG consistent with coronary vasospasm and 3 with conduction disturbances, of which one subsequently died. Patients administered oral capecitabine had a similar incidence of cardiac-related events; 1/22 (4.5%) patients with advanced breast cancer and 2/32 (6.2%) with colorectal cancer. CONCLUSIONS: The present study supports the toxic effect of 5-FU on the myocardium, which is largely schedule-dependent, whereas a low but finite risk of such toxicity has been observed with oral capecitabine. A high level of alertness is required when using fluoropyrimidines (i.v. 5FU or oral capecitabine), while their toxic effect on the coronary endothelium and myocardium merits further investigation.

Comparison of two oral regimens for the outpatient treatment of low-risk cancer patients with chemotherapy-induced neutropenia and fever: ciprofloxacin plus cefuroxime axetil versus ciprofloxacin plus amoxicillin/clavulanate.

The objective of this investigation was to assess retrospectively the safety and the efficacy of oral ciprofloxacin plus cefuroxime axetil compared to the combination of oral ciprofloxacin plus amoxicillin/clavulanate, as initial outpatient treatment, in low-risk cancer patients with fever and neutropenia. We analysed retrospectively 120 episodes of febrile neutropenia, treated on an outpatient basis at 2 different oncology units; 63 episodes were treated with the oral regimen of ciprofloxacin plus amoxicillin/clavulanate and 57 were treated with the combination of oral ciprofloxacin plus cefuroxime. 20 treatment failures were recorded-2 of them among patients receiving ciprofloxacin plus amoxicillin/clavulanate and 18 in the ciprofloxacin plus cefuroxime group. Univariate analysis showed that the administration of ciprofloxacin plus cefuroxime was associated with a worse outcome compared to the regimen ciprofloxacin plus amoxicillin/clavulanate (OR 11, CI 2.42-49.9, p =0.002). In the multivariate model, after adjusting for the absolute number of neutrophils and the duration of neutropenia, the effect of the antibiotic regimen on the outcome disappeared, and no significant differences between the 2 regimens were noted, although the regimen of ciprofloxacin plus cefuroxime was associated with a trend to a worse outcome (OR 4.74, CI 0.72-31.1, p =0.10). In conclusion, the 2 regimens appeared equally safe and effective but prospective studies are needed to confirm these results.

Docetaxel-ifosfamide combination in patients with HER2-non-overexpressing advanced breast cancer failing prior anthracyclines.

The feasibility of the docetaxel-ifosfamide combination, as well as the definition of maximum tolerated doses (MTD) in a previous phase I study, led us to continue evaluating the regimen in an extended phase II study in patients with HER2-non-overexpressing, anthracycline pre-treated advanced breast cancer. Patients with histologically confirmed metastatic breast cancer failing prior anthracycline-based chemotherapy were treated with docetaxel 100 mg/m2 over 1 h on day 1 followed by ifosfamide 5 g/m2 divided over days 1 and 2 (2.5 g/m2/day over 1 h), and recycled every 21 days with prophylactic granulocyte-colony stimulating factor (G-CSF) administration from day 3-until a neutrophil count >10,000/microl. Between March 1999 and June 2002, 71 patients with a median age of 55 years (range, 28-72) and performance status (World Health Organization; WHO) of 1 (range, 0-2) were treated; all were assessable for toxicity and 70 patients for response. Clinical response rates (RRs), on an intention-to-treat basis were: 41/71 [58%; 95% CI, 46.5-69.5%]; 7 complete remissions (CRs), 34 partial remissions (PRs), 15 stable disease (SD) and 15 progressive disease (PD). The median response duration was 7.5 months (2-28 months), median time-to-progression (TTP) 6 months (0.1-30 months), and median overall survival (OS) 12 months (0.1-36 months). Grade 3/4 toxicities included; neutropenia in 63% of patients-with 52% developing grade 4 neutropenia (>or=7 days) and in 11% of these febrile neutropenia (FN), while no grade 3/4 thrombocytopenia was observed. Other toxicities included; peripheral neuropathy grade 2 only in 7%, grade 1/2 reversible central nervous system (CNS) toxicity in 11%, no renal toxicity, grade 2 myalgias in 7%, grade 3 diarrhea in 4%, skin/nail toxicity in 11%, and grade 1/2 fluid retention in 28% of patients. The present report has demonstrated encouraging activity of the docetaxel-ifosfamide combination in anthracycline-pretreated, HER2-negative advanced breast cancer. Therefore, future randomized phase III studies versus single-agent docetaxel or currently established combinations of the latter with other agents in this setting with established clinical activity, such as capecitabine or gemcitabine, will be warranted.

A phase I-II study of bi-weekly gemcitabine and irinotecan as second-line chemotherapy in non-small cell lung cancer after prior taxane + platinum-based regimens.

PURPOSE: Treatment options in patients with recurrent non-small cell lung cancer (NSCLC) remain limited as a result of poor activity of most agents after failure of platinum-based therapy. In the present phase I-II study, we evaluated the feasibility and efficacy of bi-weekly gemcitabine (GEM) + irinotecan (CPT-11) in patients with relapsed NSCLC. PATIENTS AND METHODS: Patients with advanced NSCLC, WHO-performance status (PS)

Intramedullary spinal cord metastases from atypical small cell lung cancer: a case report and literature review.

Intramedullary spinal cord metastases (ISCM) are usually the result of rapidly progressing systemic malignancy. Lung cancer represents the most common solid tumor associated with the development of ISCM. We describe a 47-year-old female with atypical small cell lung cancer (SCLC) developing ISCM. After a thoracoscopic biopsy she was treated with combination chemotherapy consolidated by mediastinal radiotherapy leading to complete remission. Three months later, she developed a Brown-Sequard syndrome and an MRI scan revealed ISCM at the T10-T12 levels, and secondary brain lesions. Despite treatment with steroids and thoracic spine/brain radiotherapy, no recovery of her motor function was seen and she died 4 months later due to progressive disease in the CNS. The present case, adds to the existing list of ISCM cases reported so far for lung cancer, undermine the ominous prognosis and limited treatment options available, and an extensive literature overview and discussion of similar cases is provided.

Diffuse calcification of metastases after intensive multiagent chemotherapy in widespread osteosarcoma leading to death in a 18-year-old male: report of a case and literature review.

Multifocal osteosarcoma represents a rare and aggressive type of osteosarcoma in which multiple bone lesions are detected simultaneously in the absence of pulmonary or any other visceral organ involvement. Despite a multidisciplinary approach, overall survival remains poor and disease progresses, leading to death within 1 yr of diagnosis. Here we report a case of an 18-yr-old patient with extensively metastatic osteosarcoma developing diffuse calcification in lung, pleural, diaphragm, pericardial, subcutaneous metastases, and mediastinal lymph nodes after intensive multiagent chemotherapy. We provide an extensive review of the literature together with presentation of different aspects regarding the debate on the multicentric versus metastatic hypotheses for multifocal osteosarcoma. An update on the current understanding of the molecular features of this disease is also included.

A phase II study of the docetaxel-ifosfamide-carboplatin combination in advanced non-small-cell lung cancer.

PURPOSE: In the present phase II study we evaluated the docetaxel-ifosfamide-carboplatin (DICb) combination in the outpatient setting in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with advanced NSCLC (stages IIIB/IV), WHO performance status (PS) <2, and no prior chemotherapy were eligible. Chemotherapy drug doses were: docetaxel: 80 mg/m2, ifosfamide: 3.5 g/m2, and carboplatin at a target area under the curve of 5 (based on Calvert's formula), all on day 1, followed by prophylactic G-CSF. RESULTS: Fourty patients were entered and all are evaluable for response and toxicity: median age: 64 (48-72); PS: 1 (0-1); gender: 29 males/11 females; stages: IIIB: 13 (33%), IV: 27 (67%). Metastatic sites at diagnosis included: lymph nodes: 25; bone: 7; liver: 4; brain: 5; lung nodules: 13; adrenals: 6. Responses were as follows: 22/40 [55%; 95% confidence interval (CI), 54-81%] evaluable patients responded: 4 complete responses, 18 partial responses, 11 had stable disease, and 7 had progressive disease. The median response duration was 7 months (range 2-14 months), median time to progression 9 months (range 2-18 months) and median overall survival 11 months (range 3-46+ months). 1-year survival was 47.5%. Grade 3/4 toxicities included: neutropenia 28/40, with 12 developing grade 4 and 12% febrile neutropenia, thrombocytopenia grade 3: 3/40 and grade 4: 1/40, no grade 3 neuropathy, grade 1 CNS toxicity in 3, no renal toxicity, 8 grade 2 diarrhea and 4 grade 3 vomiting. CONCLUSION: In the present phase II study the DICb combination yielded important activity and good tolerability in advanced NSCLC.

Cerebrospinal fluid tumor marker levels in predicting response to treatment and survival of carcinomatous meningitis in patients with advanced breast cancer.

BACKGROUND: The aim of this study was to evaluate the predictive value of cerebrospinal fluid (CSF) tumor marker levels in patients with breast cancer and carcinomatous meningitis. MATERIAL/METHODS: Serial CSF and serum tumor marker (CEA, CA-15.3, CA-125, and CA-19.9) measurements were performed in five patients with breast cancer developing carcinomatous meningitis in an attempt to correlate these with clinical outcome under treatment. RESULTS: CSF tumor marker levels correlated with response to treatment and outcome in each patient; despite achieving negative CSF cytology after therapy, in two patients it heralded disease progression. CONCLUSIONS: Given our findings, CSF tumor marker evaluation may provide a reliable means and surrogate end-points of monitoring response of carcinomatous meningitis to treatment. Therefore, large studies to assess the value of CSF tumor marker changes in carcinomatous meningitis are warranted.

Changes of cerebrospinal fluid tumor marker levels may predict response to treatment and survival of carcinomatous meningitis in patients with advanced breast cancer.

The aim of the present study was to evaluate the predictive value of cerebrospinal fluid (CSF) tumor marker levels in patients with breast cancer and carcinomatous meningitis. Serial CSF and serum tumor marker (CEA, CA-15.3, CA-125, and CA-19.9) measurements were performed in five patients with breast cancer developing carcinomatous meningitis in an attempt to correlate these with clinical outcome under treatment. CSF tumor marker levels correlated with response to treatment and outcome in each patient, and, despite achieving negative CSF cytology after therapy in two patients, it heralded disease progression. Given our findings, CSF tumor marker evaluation may provide a reliable means and surrogate end-points of monitoring response of carcinomatous meningitis to treatment. Therefore, large studies to assess the value of CSF tumor marker changes in carcinomatous meningitis are warranted.

Irinotecan and gemcitabine in patients with advanced non-small cell lung cancer, previously treated with cisplatin-based chemotherapy. A phase II study.

BACKGROUND: To evaluate the efficacy and tolerability of irinotecan plus gemcitabine administered every two weeks in patients with advanced non-small cell lung cancer (NSCLC) previously treated with cisplatin-based chemotherapy. PATIENTS AND METHODS: Fifty patients with advanced NSCLC, refractory or resistant to cisplatin derivatives, were treated on an out-patient basis with irinotecan 150 mg/m2 intravenously (i.v.) and gemcitabine 1,800 mg/m2 i.v. on days 1 and 15, every two weeks. The response to treatment was evaluated every two cycles. The patients' median age was 59 years, 44 were men and 92% had a performance status (PS) of 0-1. RESULTS: On an intent-to-treat analysis, 8 (16%) patients, [95% confidence interval (CI), 7.2% to 29.1%] achieved partial response (PR), 19 (38%) stable disease (SD) and 23 (46%) progressive disease (PD). The median time to tumor progression (TTP) was 5.5 months (range, 0.1 to 16.5 months), the median survival time was 8.1 months (range, 0.8 to 22.1 months) and the 1-year survival 36% (95% CI, 22.9% to 50.8%). Clinical benefit response, including improvement of PS, dyspnea, anorexia and fatigue, cessation of hemoptysis and fever and reduction of cough and pain, was observed in 10% to 44% of patients. No patient experienced grade 3/4 anemia. Grade 3/4 neutropenia and thrombocytopenia occurred in 7 (14%) and 8 (16%) patients, respectively. Five (10%) patients were hospitalized due to febrile neutropenia and were successfully treated with broad-spectrum antibiotics and G-CSF support. One (2%) patient experienced grade 4 fatigue and discontinued treatment. Other grade 3/4 adverse events included diarrhea (3 cases, 2 of whom required hospitalization), alopecia (5 cases), asthenia (2 cases) and allergy (2 cases). Eight (16%) patients required a dose reduction. There were no treatment-related deaths. CONCLUSION: The combination of irinotecan and gemcitabine, administered every two weeks, demonstrated rather modest activity in advanced NSCLC patients who had previously been treated with cisplatin-based chemotherapy. It was well tolerated with mild toxicity and was associated with significant 1-year survival rate and symptomatic benefit response.