Paravasation with cyclophosphamide - Case report of tissue necrosis in a patient with primary breast cancer

Background: Paravasation is a rare but severe complication of treatment with cytotoxic agents. Some anticancer drugs are considered to be of high toxicity (vesicant), some are merely irritant, and some are regarded as nearly non-toxic to healthy tissue as is the case with cyclophosphamide. Case Report: In this report, we present the first case of severe tissue damage caused by a paravasation of cyclophosphamide in a breast cancer patient receiving chemotherapy. Conclusion: Therefore, every attending oncological physician should be aware of the possibility of severe tissue damage as a consequence of cyclophosphamide paravasation

Neutrophil 5-nucleotidase reaction in chronic myelogenous leukemia, myelofibrosis with myeloid metaplasia, and polycythemia vera

A readable and reproducible 5-nucleotidase (5N) cytochemical reaction was developed for blood smear preparation, after modification of the technique of Wachstein and Meisel [37]. The reaction was applied to normal polymorphonuclear neutrophils (NPN) and to neutrophils from patients with chronic myelogenous leukemia (CML), myelofibrosis with myeloid metaplasia (MMM), and polycythemia vera (PV). The following observations were made: (a) 5N was present in NPN, with a mean score of 83.2+/-15.7. (b) In patients with MMM and PV an increased 5N score was observed (mean score 111+/-63.8 and 178.3+/-83.3, respectively). (c) In CML the mean score was 4.9+/-2.2. (c) A statistical comparison of neutrophil 5-nucleotidase (N5N) between CML and MMM and PV patients demonstrated a highly significant difference (p<0.0001). In the present study, we showed that the N5N activity parallels that of NAP in chronic myeloproliferative disorders such as CML, MMM, and PV. It appears that, apart from the already known activity of NAP in myeloproliferative disorders, other enzymes (e.g., N5N) can present a similar behavior with increased or decreased activity

Risk of severe acute hypersensitivity reactions after rapid paclitaxel infusion of less than 1-h duration

On the basis of the safety of the 1-h paclitaxel infusion schedule in prior studies we attempted to evaluate the feasibility of a shorter infusion schedule ( < 1-h), given the general lack of published data or of attempts at applying this strategy. Before receiving paclitaxel, all patients were premedicated with promethazine, dexamethasone, and ranitidine, they were then given paclitaxel at a dose of 175 mg/m(2) diluted in 150 mi normal saline. Four patients were evaluated, two with breast cancer, one with ovarian carcinoma, and one with non-small-cell lung cancer. All had received at least two prior cycles of paclitaxel and had never exhibited any hypersensitivity reaction. In all four patients, adverse signs and symptoms were observed at 5-15 min after the start of paclitaxel administration. These included generalized erythema (three patients), angioedema tall patients), sinus tachycardia (all patients), dyspnea tall patients), and increased sweating tall patients). One patient experienced acute diarrhea. Significant changes in vital signs were recorded in all patients, but there was no dysrhythmia or syncope. Thereafter, drug infusion was interrupted and supportive measures were initiated with dimethidene maleate, ranitidine, and methylprednisolone. In ail patients, symptoms resolved over the next 15-30 min, and paclitaxel was reinstituted at the standard 1-h rate with no further sequelae. Paclitaxel administration in < 1 h did not prove to be safe in the current pilot experience and, therefore, cannot be recommended

Phase II study of paclitaxel, ifosfamide, and cisplatin as second-line treatment in relapsed small-cell lung cancer

Purpose: The aim of the present phase II study was to evaluate the efficacy of the paclitaxel, ifosfamide, and cisplatin (PIC) combination in relapsed small-cell lung cancer (SCLC), Patients and Methods: Eligible patients were those with SClC who hold progressed or relapsed after therapy with carboplatin and etoposide (with or without chest radiotherapy). The PIC regimen consisted of paclitaxel 175 mg/m(2) on day 1, ifosfamide 5 g/m(2) divided over days 1 and 2, and cisplatin 100 mg/m(2) divided over days 1 and 2; PIC was given every 21 days with granulocyte colony-stimulating factor support. Results: Thirty-three patients (30 men and three women) were entered onto the study (median age, 62 years [range, 55 to 70 years]; median performance status, 1 [range, 0 to 21). Metastatic sites at study entry included the lymph nodes (n = 13 patients), bone (n = 9), liver (n = 5), brain (n = 6), lung nodules (n = 8), adrenal glands (n = 9), and other (n = 2) Responses included eight complete remissions and 16 partial remissions (overall response rate, 73% [24 of 33 patients]). Five patients had stable disease and two had progressive disease. Median time to progression and overall survival were 21 and 28 weeks, respectively. The 1-year survival rate was 12%, with two patients alive without evidence of disease at 76 and 104 weeks since PIC initiation. Grade 3 and 4 toxicities included neutropenia in 30 patients (24 173%] developed grade 4 neutropenia [ < 5 days]) and febrile neutropenia in six patients (18%); grade 3 or 4 thrombocytopenia was seen in nine patients (27%). No grade 3 neuropathy was observed; grade 1 or 2 CNS toxicity was seen in five patients, there was no renal toxicity, grade 2 myalgias were seen in nine patients, grade 2 diarrhea was seen in one patient, and grade 3 nausea or vomiting was seen in seven patients. There were no treatment-related deaths. Conclusion: In the present phase II study, the PIC combination seemed highly active and tolerable in patients with relapsed SCLC when it was administered as second-line treatment. Given the present experience, an evaluation of the PIC regimen as front-line treatment of SCLC is planned. J Clin Oncol 19:119-126. (C) 2001 by American Society of Clinical Oncology

Extragonadal seminoma after renal transplantation and immunosuppression; Treatment in the presence of renal dysfunction - A case report and literature review

A 37-yr-old man who had undergone renal transplantation for end-stage renal failure presented with a large right pelvic mass obstructing the transplanted kidney. Initially, this was diagnosed as an anaplastic tumor while he had been on immunosuppressive treatment for kidney allograft rejection after transplantation. Despite difficulties of classic histopathology to reveal the origin of his tumor, FISH analysis revealed the presence of chromosome 12p abnormalities, strongly indicative of a germ-cell tumor-more likely seminoma-with extragonadal presentation. Because of renal dysfunction, he was treated with carboplatin (dose adjusted according to renal clearance) and etoposide, and when he experienced a rather atypical progression with bone metastases, he was treated with single-agent paclitaxel, and died almost 13 mo after initial presentation. The case adds further to the existing small list of seminoma/GCTs developing in transplant recipients, points to the unusual presentation patterns and diagnostic histopathology challenges; and presents the difficulty in therapeutic options, as a result of frequent renal dysfunction and intercurrent immunosuppressive therapy. All of these issues together with an extensive litterature review are discussed in detail

Antiemetic prophylaxis with ondansetron and methylprednisolone vs metoclopramide and methylprednisolone in mild and moderately emetogenic chemotherapy

The purpose of the present study was to examine whether its is possible to successfully replace ondansetron (OND) with metoclopramide (MCP) in patients examined to moderately emetogenic chemotherapy who did not experience severe nausea and vomiting while undergoing OND treatment during their first chemotherapy cycle. After switching to MPC, patients continued with this drug for three cycles, provided that they had adequate control of nausea and vomiting. Otherwise, they were switched back to OND. There were 76 patients, 60 women and 16 men, whose median age was 56 (mean 58) years. Karnofsky performance status score was 100 in 18 patients, 90 in 23, and 80 in 11 patients. No patient had previous chemotherapy Thirty-four patients had breast cancer and received fluorouracil 500 mg/m(2) epirubicin 100 500 mg/m(2), and cyclophosphamide 500 mg/m(2). Twelve patients had small cell lung cancer and received carboplatin 400 mg/m(2) + etoposide 120 mg/m(2) X 3 days. Twenty patients with ovarian cancer received carboplatin 350 mg/m(2) and cyclophosphamide 500 mg/m(2). Ten patients had cancer of unknown primary and received carboplatin 400 mg/m(2), epirubicin 60 mg/m(2), and etoposide 120 mg/m(2) X 3 days. The OND schedule consisted of methylprednisolone 40 mg intravenous bolus followed by OND 8 mg in a 15-min infusion before chemotherapy followed by OM) 4 mg orally X 3 on the same and the next 2 days. Patients who did not experience nausea and vomiting with OND continued with an MCP schedule consisting of methylprednisolone 40 mg bolus followed by MCP 2 mg/kg in a 15-min infusion before chemotherapy, followed by MCP (20 mg X 4 on the day of therapy and the next 2 days after). Patients who failed with MCP or OND) continued with OND. Considering our results as a whole, the intensity of nausea does not appear to influence the results of Gralla’s scale. The results of Gralla’s scale do not appear to be affected by the analysis of the antiemetic results and nausea on the next 2 days following chemotherapy administration. Overall patients received 145 cycles with OND and 159 cycles with MCP. Of the 76 patients receiving OND-based antiemetic regimen during the first cycle, 13 (21%) experienced severe vomiting (Grade 2, 3) and the remaining 63 (79%) had mild or no vomiting (Grade 0, 1). Patients with Grade 0, 1 vomiting (63, 83%) continued with MCP in the second cycle. The final number of patients who failed on MCP after 4 cycles of chemotherapy increased to 33 (43 %); 43 (57 %) were able to complete chemotherapy with MCP. Headache occurred in 15 (10 %) cycles with OND and 8 (5 %) with MCP. Flushing was noted in 12 (8 %), and constipation occurred in 43 (30 %) of OND cycles, and extrapyramidal manifestations occurred in 3 (5 %) of patients receiving MCP. Diarrhea was noted in 3 (2 %) of cycles with OND and in 28 (18 %) with MCP. The cost ratio between MCP and OND wets 1:14. If we administered OND only in patients who needed it, the overall cost decreased to 44 %. Following the strategy applied in the present study, the cost decreased to 47 %. (C) U.S. Cancer-Pain Relief Committee, 1999

Granulocyte-macrophage colony-stimulating factor improves immunological parameters in patients with refractory solid tumours receiving second-line chemotherapy: Correlation with clinical responses

In this report, we studied the immunorestorative properties of subcutaneously administered granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with refractory solid tumours receiving second-line chemotherapy. Such patients exhibit abnormal immune responses in vivo and in vitro and, therefore, it was of interest to examine the effect of GM-CSF-induced immunomodulation on clinical response. We examined patients with primary malignant carcinomas (head and neck, n = 10; urogenital tract, n = 17; penis n = 6; colorectal, n = 8) who were treated with carboplatin (JM8), 300 ng/m(2) on days 1 and 22, leucovorin (LV), 200 mg/m(2) plus 5-fluoracil (5-FU), 500 mg/m(2) on days 8, 15 and 29 and four cycles of daily injections with placebo or GM-CSF, 300 mu g/day on days 3-6, 10-13, 17-20 and 24-27. Peripheral blood was collected from the patients one day after the end of each of the four-cycle injections with placebo or GM-CSF, namely on days 7, 14, 21 and 28. Peripheral blood mononuclear cells (PBMC) were tested in the autologous mixed lymphocyte reaction (AMLR) and for natural killer (NK) or lymphokine-activated killer (LAK) cell activity. Cytokine levels in serum were measured by immunoenzymatic (ELISA) assay. A total of 21 patients received a four-cycle regimen with GM-CSF (Group 1) and 20 were similarly treated with placebo (Group 2). All received standard chemotherapy as outlined above. Before GM-CSF treatment, all patients exhibited increased serum levels of interleukin-1 (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), IL-6 and prostaglandin E-2 (PGE(2)) and decreased serum levels of IL-2. Cellular immune responses (AMLR, NK- and LAK-cytotoxicity) were also low in all patients. Five patients from Group 1 had a PR (partial response), 2 patients had CR (complete response), and 14 patients had stable disease. Seven patients from Group 2 showed progressive disease, 3 had a PR and 10 had stable disease. All immune parameters were significantly improved during treatment in Group 1 but remained unchanged or even deteriorated in Group 2. Administration of GM-CSF during treatment of cancer patients with conventional chemotherapeutic drugs results in a marked potentiation of deficient cellular immune responses in vitro and a change towards normalisation of cytokine serum levels. The results reported herein support the use of GM-CSF as immunopotentiator during chemotherapy, but more patients must be studied before definite conclusions can be drawn. (C) 1997 Published by Elsevier Science Ltd