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PubMed1985

Mitomycin-C nephrotoxicity: a clinico-pathologic study of 17 cases.

The potential nephrotoxicity of Mitomycin-C (MMC) was studied in 17 autopsies from patients treated with this drug, usually in association with other anti-neoplastic agents. Renal functional deterioration was present in seven cases while urinalysis showed an overt proteinuria and hematuria in six and four instances, respectively. Four of these patients also developed a severe microangiopathic hemolytic anemia (MAHA) and thrombopenia. Histological examination did not reveal residual tumor in three of them. However renal lesions similar to those observed in the hemolytic-uremic syndrome (HUS) were associated with glomerular mesangiolytic changes and nuclear atypias in glomerular and tubular cells. Immunofluorescence and ultrastructural studies confirmed these findings. In other patients, variable degrees of cellular atypias and of mesangiolysis were observed. The severity of the glomerular, vascular, and tubular lesions correlated with the total dosage of MMC received. The nephrotoxic potential of MMC seems to be delayed in onset and dose related.

Adult↗
PubMed2000

[The prognostic factors of invasive pulmonary aspergillosis in patients with chronic pneumopathy].

OBJECTIVES: a) To determine in patients with chronic respiratory disease the risk factors for death due to semi-invasive and invasive pulmonary aspergillosis (SIPA), and b) to describe the clinical features of SIPA in such patients. METHOD: Twenty-one patients with chronic respiratory disease were enrolled (9 with chronic obstructive pulmonary disease, 2 asthmatics and 3 with bronchiectasis, 5 with post-tubercular sequelae and 2 mixed cases). A diagnosis of SIPA was established in our hospital when, in a patient with a clinical picture consistent with such a diagnosis, the fungus was isolated in bronchial secretions or parenchymal pulmonary specimens were obtained during autopsy. RESULTS: The most common symptoms were dyspnea (81%), cough (67%) and expectoration (62%) increasing over the levels usual for patients with chronic respiratory disease. Hemoptysis was present in only 14%. Eight patients (38%) died as a result of SIPA. A comparison of those surviving and non-surviving patients revealed that the latter had significantly higher LDH levels and white cell counts, and significantly lower total plasma protein and platelet counts. CONCLUSIONS: a) Low protein levels and high LDH levels and white cell counts with thrombopenia are indicators of poor prognosis in chronic respiratory disease patients with SIPA, and b) such patients do not usually present signs or symptoms that lead to a suspicion of SIPA given that such signs are typical of failing compensatory mechanisms in the disease itself.

Aged↗
PubMed2001

[Acute myocardial infarction in nocturnal paroxysmal hemoglobinuria].

The case of a 62-year-old diabetic and smoker male who was under study in another hospital due to anemia, thrombopenia and hematuria of several months of evolution is presented. The patient was admitted to the coronary unit for an acute extensive transmural myocardial infarction and treated with t-PA. A few hours later the patient presented hematuric urine, a decrease in hemoglobin and platelets and acute renal insufficiency. Hematologic study confirmed the diagnosis of paroxystic nocturnal hemoglobinuria. The evolution of the patient was poor despite intensive medical treatment requiring hemodialysis. The patient presented cardiac tamponade and died. The role of hematologic disease in acute myocardial infarction and the treatment and evolution of the coronary syndrome in the context of the disease are discussed.

Hemoglobinuria, Paroxysmal↗
PubMed2003

Spontaneous rupture of non-tumoral kidneys in patients with end stage renal failure: risks and management.

OBJECTIVES: To determine the risks and treatment modalities of spontaneous subcapsular or perinephric bleeding in end stage renal patients. METHODS: 8 patients with end stage renal failure developed a spontaneous hemorrhage of one of their native kidneys and were referred to our institution. They were all men. Six of them presented an acquired renal cystic disease. Symptoms included sudden abdominal pain in 7 patients, vomiting in 2 and hematuria in 1. Symptoms were always associated with a hemoglobin decrease. Four patients were receiving oral anticoagulants for various reasons and one had thrombopenia. Bleeding was confirmed by computerized tomography and nephrectomy undertaken in all cases. RESULTS: 3 patients died in the immediate post-operative period. Histologic findings confirmed bleeding and did not find any other abnormality than those related to renal insufficiency (cysts and atrophy). CONCLUSION: Renal rupture should be considered in case of unexplained distress or sudden fall of the hemoglobin especially when patients are on anticoagulants. Surgery is our preferred treatment because of the frequency of unrevealed tumours and the potential mortality of massive hematomas.

Adult↗
PubMed2003

Postoperative adjuvant gemcitabine and concurrent radiation after curative resection of pancreatic head carcinoma: a phase II study.

PURPOSE: The addition of radiation to adjuvant 5-fluorouracil for the treatment of pancreatic cancer has not yet shown any definite benefit. Gemcitabine (GEM) has potential activity in advanced pancreatic cancer and is a powerful radiosensitizer. We evaluated the feasibility of postoperative administration of GEM alone, followed by concurrent GEM and irradiation (RT) after curative resection for pancreatic adenocarcinoma. METHODS AND MATERIALS: GEM 1000 mg/m(2) on Days 1 and 8 every 21 days for three courses was given within 8 weeks after surgery and was followed by GEM 300 mg/m(2) weekly +40 Gy in a split course. Twenty-two patients (median age 59 years, range 39-74, Performance Status 0-1) with Stage II and III curatively resected pancreatic head adenocarcinoma were included. RESULTS: For GEM alone, all patients received the three planned courses, with dose reductions in 7 (32%) of 22 patients. All patients, except two, completed full chemoradiation; one received only 20 Gy because of both World Health Organization Grade 4 vomiting and thrombopenia and the other stopped RT after 32 Gy because of early disease progression. No reduction in GEM during RT was necessary; no toxic death was noted; and World Health Organization Grade 3-4 hematologic and nonhematologic toxicities occurred in 8 (36%) and 7 (nausea, vomiting) (32%) of 22 patients respectively. No late toxicity developed. After a median follow-up of 15 months, 11 patients were alive, and 2 patients had died of causes unrelated to their disease or toxicity, The median disease-free survival and overall survival was 6 and 15 months, respectively. CONCLUSION: This adjuvant regimen was well tolerated and can be easily administered after curative surgery for pancreatic cancer. Its intensification with continuous RT is currently being investigated.

Adenocarcinoma↗
PubMed2001

[Chronic experimental bacteremia in Yucatan micropigs].

The Yucatan micropig has been used to develop an experimental model of chronic bacteremia. This animal exhibits clinical and biological characteristics that are close to those in humans, and the pharmacokinetic behaviours of many classes of drugs in this model are similar to those in man. Six adult female were intravenously inoculated with a mean Escherichia coli inoculum of 5.1 x 10(9) bacteria. During five days of spontaneous evolution, the medical follow-up includes biological, clinical and bacteriological parameters. A systemic inflammatory syndrome, a sepsis, an organ insufficiency and positive blood cultures mimic the human disease. In all animals there is an adynamia, a lack of motor coordination, an anorexia, a tachypnea, a fever, a leuconeutropenia followed by an hyperleucocytosis, an anemia, a thrombopenia, an acute tubulonephritis and an elevated sedimentation rate. In some cases, there is an increase of the C reactive protein, in others, an increase of IL-6 and IL-8. At day five, all animals are alive, and five micropigs have positive blood cultures. This chronic, reproducible model is thus suitable for further antibacterial treatments evaluations.

Acute Kidney Injury↗
PubMed2005

[Does antiaggregant therapy have a place in type II heparin-induced thrombocytopenia?].

We report a case of type II heparin-induced thrombocytopenia, which occurred after heart surgery in a 71-year-old female patient with several cardiovascular risk factors. The diagnosis of heparin-induced thrombopenia was suspected because association of multifocal arterial and venous thrombosis and detection of antiplatelet-factor 4 antibodies with a drop of more than 50% in the platelet count. Until diagnostic of heparin-induced thrombocytopenia was made, clopidogrel was introduced because of well-documented ischemia in middle-cerebral artery territory. The platelets subsequently increased by near 30%. The diagnosis of heparin-induced thrombocytopenia was finally confirmed a few days later by detection of antiplatelet-factor 4 antibodies associated with a positive platelet aggregation test for unfractionated heparin. Heparin was replaced by sodium danaparoid. These measures did not change the unfavorable outcome and death of the patient. The increase in the platelet count after fortuitous clopidogrel introduction raises the question of the role of antiaggregant agents in association with anticoagulants for the treatment of type II heparin-induced thrombocytopenia.

Aged↗
PubMed1999

[Antiphospholipid antibody syndrome in pediatric neurosurgery: a hemostasis problem].

The case of a 11-year-old boy under anticoagulant therapy for a familial antiphospholipid antibody syndrome (SAAPF), who underwent surgery for a cerebrovascular malformation responsible for an intracerebral haematoma, is reported. Antivitamins K (AVK) were changed for unfractioned heparin (HNF), three days before. Heparin was discontinued two hours prior to surgery to obtain a normal peroperative coagulation. A vascular dural fistula was removed without any haemostatic problem. The neurological status rapidly returned to normal and tomodensitometry at day 1 showed a normal intracranial status. Heparin was readministered at h 16. Thrombocytopenia occurred at day 4 of heparin treatment. The change for a low weight molecular heparinoid, danaparoid (Orgaran), normalized the platelet count. The platelets aggregation tests were negative during thrombopenia. However, the test for antibodies against the PF4-heparin complex with the Elisa technique, was in favour of a heparin induced thrombocytopenia (TIH). In spite of its anecdotic occurrence due to cumulative thrombotic risks from the association of immunologic disorders (TIH and SAAPF), this case report underlines the value but also the risks of anticoagulant therapy in neurosurgery, when patients are at high risk for thrombosis.

Antiphospholipid Syndrome↗
PubMed2003

[Value of a long duration temporary caval filter in critical thrombo-embolic situations].

In the event of proximal venous thrombosis with a risk of pulmonary embolism, contraindications to or complications of anticoagulant treatment are not uncommon in surgical or intensive care units. These are worrying but temporary situations and represent a classic indication for partial interruption of the inferior vena cava, for which permanent caval filters are not usually suitable. Temporary filters are an attractive option in this context, as long as they are safe and stable, can be left in place long enough to permit normalization of the thrombosis and anticoagulation problems and can then be removed in all circumstances, whether or not they have trapped a thrombus while in place. Most temporary filters do not meet all these criteria and nor do permanent filters with a removal option. We tested the new Tempofilter II filter with increased stability, which has a smooth geometry and can be implanted for up to 6 weeks, in 13 patients. We selected two documented cases concerning, firstly, a contraindication to anticoagulants and, secondly, recurrent thrombosis in heparin-induced thrombopenia. In both cases, the filter trapped a thrombus and prevented a pulmonary embolism, which would have been poorly tolerated and difficult to treat. The filters were removed without any difficulty after 4 and 6 weeks. We did not observe any complications related to infection or migration. Monitoring is recommended throughout the implantation period, in order to identify any clots trapped in the filter and to monitor their lysis or non-emboligenic fibrous structure, authorising removal of the filter.

Aged↗
PubMed1998

Biological activities and clinical application of M-CSF.

Macrophage colony-stimulating factor (M-CSF) was found to be a glycoprotein with a molecular weight of 85 kDa which stimulated macrophage colony formation of mouse bone marrow cells in a semisolid agar culture system in 1978. M-CSF stimulates differentiation of progenitor cells to mature monocytes, and prolongs the survival of monocytes. It enhances expression of differentiation antigens and stimulates chemotactic, phagocytic and the killing activities of monocytes. Macrophage CSF also stimulates production of several cytokines such as granulocyte-macrophage CSF, granulocyte CSF and interleukin (IL)-6 by priming monocytes, and directly stimulates production and secretion of IL-8 and reactive nitrogen intermediates. In addition to the stimulation of hematopoiesis, M-CSF also stimulates differentiation and proliferation of osteoclast progenitor cells and cytotrophoblasts. Proteoglycan type M-CSF, which contains chondroitin sulfate chains, was found in 1992. In a large-scale double-blind controlled study on acute myeloid leukemia (AML), it has been shown that the administration of M-CSF to patients after consolidation chemotherapies shortens the periods of neutropenia and thrombopenia after chemotherapy and reduces the incidence and shortens the duration of febrile neutropenia, as well as shortening the period required to finish three courses of intensive consolidation therapy.

Humans↗
PubMed1997

Hematopoietic stem cell expansion.

This review addresses two issues: (1) cytokine-mediated expansion of functional end cells for the abrogation of short term neutropenia and thrombopenia following high dose chemotherapy and (2) cytokine-driven increase in absolute numbers of functional stem cells. The literature suggests that the short term exposure of CD34+ cells to cytokines produces mature progenitors which in turn give rise to functional neutrophils and platelets. The expansion of functional stem cells is a more complex issue, as primitive stem cells are quiescent and their growth requirements are less clearly defined.

Animals↗
PubMed2000

Up-front chemotherapy with fotemustine (F) / cisplatin (CDDP) / etoposide (VP16) regimen in the treatment of 33 non-removable glioblastomas.

Despite combinations of surgery, radiotherapy (RT) and chemotherapy used in the treatment of glioblastomas, mean and median survival rates in most patients remain 12 months or less after diagnosis. RT and nitrosourea after surgery are the standard combination for glioblastomas. They may induce acquired resistance and, consequently, non-operable glioblastomas is a unique biological and clinical situation allowing evaluation of intrinsic chemosensitivity. We assess the fotemustine (F) (100 mg/m2 day 1)/ cisplatin (CDDP) (33 mg/m2 days 1-3)/etoposide (VP16) (75 mg/m2 days 1-3) monthly regimen for efficacy in non-removable glioblastomas at presentation. Between 1995 and 1998, 33 consecutive patients with symptomatic non-removable histologically proven glioblastomas were treated: none of them had previously received chemotherapy, irradiation or surgical debulking. Objective response was evaluated by contrast enhancement with magnetic resonance imaging (MRI) scan after each treatment. Toxicity was moderate and mainly haematological (grade III-IV thrombopenia = 20/171 cycles; leucopenia = 25/171). Neutropenic fever was rare and no intracranial haemorrhages or treatment-related deaths were noted. Nausea and vomiting (grade 1), and asymptomatic hearing loss were common. Peripheral neuropathy occurred in 3 patients. Objective response rates were 9/33 (27%) (stabilisation = 17/33). Mean survival time was 14.4 (11.2 months in the 26 deceased patients) with a median survival of 10 months. Median survival rates at 6 and 12 months were 88% and 42%, respectively. 7/33 patients are still alive with median survival of 34.6 months. 7/33 (4/7 alive) were long-term survivors (range: 19-67 months). Neoadjuvant chemotherapy in non-resectable patients is safe allowing delayed RT. Phase II chemotherapy trials should include studies with a subgroup of non-resectable tumours.

Adult↗
PubMed1993

Phase I study of WR-2721 and carboplatin.

Because WR-2721 reduces the toxicity of cisplatin and carboplatin in preclinical systems, we have treated 35 patients in a phase I study of WR-2721 and carboplatin. As the plasma half-life of WR-2721 is short relative to that of carboplatin, WR-2721 was administered in two divided doses. This schedule produced acceptable toxicity in 24 patients treated with carboplatin 400 mg/m2 and escalating doses of WR-2721. In the subsequent 11 patients, WR-2721 was fixed at 740 mg/m2/dose and the dose of carboplatin was escalated. With WR-2721, grade 3-4 thrombopenia (platelets < 50 x 10(9)/l) was produced in 4/5 patients treated with carboplatin 625 mg/m2 and in 1/6 patients treated with carboplatin 500 mg/m2. Carboplatin pharmacokinetic parameters in 4 patients were similar to those reported for carboplatin alone. These results suggest that WR-2721 might increase the maximum tolerated dose of carboplatin from 400 to 500 mg/m2.

Adult↗
PubMed1997

Oxaliplatin/cisplatin (L-OHP/CDDP) combination in heavily pretreated ovarian cancer.

The aim of this study was to evaluate the toxicity and the activity of two non-cross-resistant platinum compounds: oxaliplatin (L-OHP) and cisplatin (CDDP) in platinum pretreated ovarian cancer patients. Chemotherapy consisted of L-OHP and CDDP given sequentially as 2 h infusions on day 1 at their standard recommended dose (130 mg/m2 for oxaliplatin, 100 mg/m2 for cisplatin) every 3 weeks. Dose reductions (20-35%) were planned according to baseline haematological and renal status, but the dose ratio between L-OHP and CDDP was always maintained at 1.3. Cycles were repeated until progression or treatment limiting toxicities. From September 1992 to November 1994, 25 patients with pretreated ovarian cancer entered this salvage programme. They had received a median number of three previous chemotherapy lines (1-7), one at least platinum based. Previously cisplatin had been given to 22 patients at a median total dose of 600 mg/m2 (170-1175), while 18 had received carboplatin to a median total dose of 1135 mg/m2 (200-2450). 9 patients had also received and were resistant to taxanes (paclitaxel, 6 patients, docetaxel, 3 patients), while the rest were considered ineligible for simultaneously ongoing single-agent taxane phase II trials. 13 and 12 patients, respectively, were considered to have platinum refractory and potentially sensitive disease, according to Markman's criteria. 77 cycles of L-OHP/CDDP were given, with a median of three cycles/patient (range 1-6) and were evaluable for toxicity. The limiting toxicity of the L-OHP/CDDP combination was a cumulative, sensory peripheral neuropathy, severe (> or = grade 3 CTC) after more than three cycles, but reversible within a few months of its discontinuation. Grade 3-4 (WHO scale) neutropenia and thrombopenia were seen in 35-40% of cycles, with one neutropenic treatment-related death (septic shock). 22 patients with measurable/evaluable disease were assessable for antitumoral activity. Two complete responses (CR) (8%) (one proven histologically at laparotomy (pCR)) and 8 partial responses (PR) (32%) for an overall objective response rate (ORR) of 40% (95% CI, 21-61%) (intent to treat). The median duration of response was 4 months. Seven responses were seen among 12 potentially platinum-sensitive tumours (58%, CI 95% 28-85%), while 3/13 platinum refractory patients (23%, CI 95% 5-54%) had an objective response. These encouraging results are the basis for new first- and second-line combination treatment programmes in ovarian carcinoma.

Adult↗
PubMed1999

A comparison of methods of calculation for estimating carboplatin AUC with a retrospective pharmacokinetic-pharmacodynamic analysis in patients with advanced non-small cell lung cancer. European Lung Cancer Working Party.

We retrospectively analysed the data obtained in a large randomised trial performed in 505 eligible patients with advanced non-small cell lung cancer. Its purpose had been to compare a combination of carboplatin (200 mg/m2) and cisplatin (60 mg/m2) with or without the addition of ifosfamide. The present retrospective analysis assessed two ways of dosing carboplatin: according to body surface area (mg/m2) or to the estimated targeted area under the concentration versus time curve (AUC). Two different methods were used in the latter calculation: the Calvert formula using the Cockroft approximation to evaluate the glomerular filtration rate and the Chatelut equation. There was an excellent linear correlation between them. With the Chatelut method, the calculated administered AUC were lower. Whichever method was used, carboplatin AUC was not significantly associated with antitumour response rate nor patient survival. A statistically significant increase in haematological toxicity, mainly thrombopenia, was observed with an increase in the AUC. This effect was observed whatever AUC variable was considered, i.e. total dosage at course one, total dosage during the first three chemotherapy courses or dose intensity during the first three courses. The effect remained highly significant after adjustment for treatment arm. We conclude that for a moderate carboplatin dose in non-small cell lung cancer, the therapeutic index could be improved if dosage is calculated according to the AUC.

Adult↗
PubMed1997

[Concomitant radiochemotherapy in inoperable non-small cell lung cancer].

PURPOSE: As locally advanced and inoperable non-small cell lung cancers still have a poor prognosis, the present phase II study focused on the administration of concomitant chemotherapy and radiotherapy and was aimed at increasing both local and metastatic controls. MATERIALS AND METHODS: Thirty-nine patients (36 male and three female patients, mean age, 56 years) were included into the study. Ninety five percent of them had a good performance status (OMS status 0 or 1). The histopathological analysis showed the existence of squamous cell in 64% of the cases. There was one stage I tumor, nine stage IIIA tumors and 24 stage IIIB tumors. In two cases, the tumor stage was unknown. The duration of each cycle of the protocol was 3 weeks and included the administration of cisplatin (50 mg/m2 at d1 and d2) and fluorouracil (5-FU) (1 gr/m2 in continuous infusion at d1, d2, and d3), and external beam irradiation (20 Gy subdivided into 2 Gy-fractions that were administered from d1 to d12); the 3rd week was a resting period. RESULTS: The tolerance to the treatment was good. Fifteen per cent grade 3-4 leucopenia, 3% grade 3-4 thrombopenia and 15% grade 3-4 nausea with vomiting were observed. No serious esophagitis was recorded. Chemotherapy was completed in more than 90% of the cycles. An objective response was described in 56% of the cases, with only 3% of complete responses. However, evaluation was done on average 6 weeks after radiotherapy, at a time where post-irradiation fibrosis could hamper radiological assessment. Median survival and 2- and 3-year survivals were 11.4 months, 27% and 14%, respectively. The only significant prognostic factor was the OMS performance status index, while the radiological response was particularly non-predictive of survival. Failure patterns were analyzed in 20 patients and consisted of the following: local relapse only, six cases; metastatic relapse only, 13 cases; both local and metastatic relapse, one case. CONCLUSION: The concomitant administration of 5-FU, cisplatin and external irradiation seems feasible in current clinical practice. Survival but not radiological response should be the only criteria to evaluate this type of association. Improvement in local control is not unlikely with this type of association.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

[Tolerance and role of irradiation in the treatment of epithelial cancer of the ovary].

PURPOSE: In a retrospective analysis, our aim was to evaluate the immediate tolerance and the early and late complications of abdomino-pelvic radiotherapy in the Centre Alexis-Vautrin (France). PATIENTS AND METHODS: From 1st January 1983 to 31st December 1993, 117 patients were treated at Centre Alexis Vautrin in Nancy for epithelial ovarian cancer by abdominal and/or pelvic irradiation after surgery. They were aged from 24 to 85 with a median of 56 years. There were ten patients with stage I (9%), 28 patients with stage II (24%), 60 patients with stage III (61%) and 19 patients with stage IV (16%) disease. Results of surgery were determined as follows: satisfactory with absence of tumoral residuum in 26% cases (30 patients) and with residuum inferior to 20 mm in 46% cases (52 patients; incomplete in 26% cases (31 patients) either because of residuum superior in 20 mm and/or incomplete surgery; and not evaluable in 3% cases (four patients). Seventy-seven patients were sent to the Centre for postoperative treatment (66% patients of the series), 48 of them (62.4%) after non-satisfactory surgery, 29 after satisfactory surgery (37.6%). Chemotherapy was administered to only 104 patients (89% cases), and contained platinum salts and cyclophosphamid for 87% of these patients. Fourteen patients (12%) received a single irradiation dose after surgery: three in stage I, three with poor evaluation of the disease in the initial stage, three with medical contraindications to chemotherapy treatment, six with contraindications due to advanced age (?? Makes 15 ). Histologically, 46% of patients had a serous adenocarcinoma, 9% a mucinous adenocarcinoma, 11% an endometrioid adenocarcinoma, 2% a clear cell adenocarcinoma, 1% an undifferentiated adenocarcinoma, and 31% an epithelial carcinoma without any other indication. The histological grade which was recently introduced was rarely indicated. Complementary radiotherapeutic treatment consisted of pelvic irradiation for 14 patients (12%), abdomino-pelvic irradiation for 63 patients (54%), and total abdominal irradiation with a pelvic boost for 40 patients (34%). RESULTS: The immediate tolerance to irradiation can be considered as globally satisfactory since 9% of the patients (ten cases) had no problems and 64% of the patients developed a minor intolerance easily controlled by symptomatic treatments. There were also digestive complications: nausea, vomiting and diarrhea for 66% of the patients (50 cases); to a lesser extent, 20% of the cases experienced associated digestive and hematological complications (15 patients); 9% isolated hematological troubles such as anemia (seven patients); 4% digestive complications (three patients) and 1% hematological and urinary digestive troubles (one patients). Late irradiation sequelae were evaluated for 89 patients with a follow-up lasting from 4 months to 11 years. Sixty-six patients had no sequelae, eleven patients had minor tolerability problems--mainly digestive for more than half of them. Five patients presented severe complications, including hematological problems such as chronic thrombopenia in two cases, urinary-problems in two other cases, and one patient presented with a case of histologically proven malabsorption. Two patients presented major problems; one case of radic cystitis and one of radic bowel. Two patients died of iatrogenic causes: one of induced leukemia, the other of treatment-induced digestive and renal complications. The overall survival rate was 30% at 5 years and 22% at 10 years. It was 90% at 5 and 10 years for stage I patients, 60% at 5 years and 30% at 10 years for stage II patients, 22% at 5 years and 8% at 10 years for stage III patients, and finally 10% at 5 years for stage IV patients. CONCLUSION: In this retrospective analysis of 117 epithelial ovarian cancers, treated over 10 years and which all received pelvic and/or abdominal irradiation, we can conclude that this treatment is globally well tolerated and that it yields a

Adenocarcinoma↗
PubMed1997

Experience with intraperitoneal cisplatin and etoposide and i.v. sodium thiosulphate protection in ovarian cancer patients with either pathologically complete response or minimal residual disease.

BACKGROUND: High-dose platinum-based regimens can produce responses in patients not responding to standard chemotherapy. As in many ovarian cancer patients the disease remains confined to the peritoneal cavity, intraperitoneal (i.p.) chemotherapy has been applied as an alternative approach to increase drug exposure. The delivery of cytotoxic agents to the peritoneal cavity can lead to high drug concentrations intraperitoneally with less systemic toxicity. This study aimed at evaluating the efficacy and toxicity of high-dose i.p. cisplatin plus etoposide and intravenous sodium thiosulphate protection in ovarian cancer. PATIENTS AND METHODS: Patients with either a pathologically complete response (pCR) after first-line treatment or with persistent disease after first-line platinum-based chemotherapy or abdominal recurrences were eligible. All intraabdominal lesions had to be < 2 cm at the start of i.p. treatment. The treatment consisted of etoposide 350 mg/m2 i.p. followed by cisplatin 200 mg/m2 i.p. with intravenous sodium thiosulphate (4 g/m2 bolus, followed by 12 g/m2 over six hours) protection. Four courses of i.p. treatment were administered in case of pCR and 6 courses otherwise, at four-weekly intervals. RESULTS: The study comprised 29 patients, six patients with pCR, 17 patients with persistent disease and six patients with abdominal recurrences. They received a total of 105 courses of treatment (65% of the scheduled number of courses). Twelve patients completed scheduled treatment, illustrating its feasibility. In 17 patients treatment had to be prematurely stopped because of inflow obstruction (seven patients), bowel perforation (two patients), renal toxicity (two patients), neurotoxicity (two patients), or malaise and vomiting (four patients). One patient with bowel perforation died of this complication. Severe nausea and vomiting occurred in 51% of cycles. Leukopenia and thrombopenia grade 3 and 4 occurred in 30% and 6% of cycles, respectively. Ototoxicity of cisplatin was measured by serial tone audiography in 23 patients: only eight patients (35%) showed significant audiographic changes, although none of them developed clinical hearing loss. Fifteen patients were evaluable for response: four pCR, five PR, two SD, four PD. The median duration of freedom from progression was 616 days and the median overall survival 1065 days from the start of treatment. CONCLUSIONS: High-dose i.p. treatment with cisplatin and etoposide can be associated with significant toxicities. Major clinical problems are nausea, vomiting, and the formation of intraabdominal adhesions. Intravenous sodium thiosulphate effectively reduces the systemic toxicity of high-dose cisplatin. The value of high-dose i.p. treatment is uncertain and its routine use cannot be recommended.

Adult↗