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A Thyss

Publications and source records attributed to A Thyss.

At least 55 records · Page 3Linked to original sources
PubMed1998

High-dose methotrexate for the treatment of primary cerebral lymphomas: analysis of survival and late neurologic toxicity in a retrospective series.

PURPOSE: The impact of treatment options on survival and late neurologic toxicity was investigated in a series of patients with primary cerebral lymphoma (PCL) and no known cause of immunosuppression. PATIENTS AND METHODS: Prognostic factors for survival and treatment-induced late neurotoxicity were investigated in a retrospective series of 226 patients with PCL. RESULTS: With a median follow-up of 76 months, the median overall survival was 16 months and 5-year survival was 19%. In a univariate analysis, age greater than 60 years, performance status, CSF protein level greater than 0.6 g/L, involvement of corpus callosum or subcortical grey structures, detectable lymphoma cells in CSF, increased serum lactate dehydrogenase (LDH), but not histological subtype, were significantly correlated with a poor survival. Treatment with chemotherapy versus radiotherapy alone (P = .05), high-dose methotrexate (HDMTX; P = .0007), and cytarabine (P = .04) correlated with a better survival in univariate analysis. Using the Cox model, age, performance status, and CSF protein were independently correlated with survival. After adjustment of these factors, treatment with an HDMTX-containing regimen remained the only treatment-related factor independently correlated with survival (P = .01). The projected incidence of treatment-induced late neurotoxicity was 26% at 6 years in this series, with a median survival from the diagnosis of late neurotoxicity of 12 months. Treatment with radiotherapy followed by chemotherapy was the only parameter correlated with late neurotoxicity in multivariate analysis (relative risk, 11.5; P = .0007). CONCLUSION: Patients with PCL treated with regimens that included HDMTX followed by radiotherapy have an improved survival, but not a higher risk of late neurotoxicity as compared with other treatment modalities in this series.

Adolescent↗
PubMed1998

Mitoxantrone versus daunorubicin in induction-consolidation chemotherapy--the value of low-dose cytarabine for maintenance of remission, and an assessment of prognostic factors in acute myeloid leukemia in the elderly: final report. European Organization for the Research and Treatment of Cancer and the Dutch-Belgian Hemato-Oncology Cooperative Hovon Group.

PURPOSE AND METHODS: Optimization of remission-induction and postremission therapy in elderly individuals with acute myeloid leukemia (AML) was the subject of a randomized study in patients older than 60 years. Remission-induction chemotherapy was compared between daunomycin (DNR) 30 mg/m2 on days 1, 2, and 3 versus mitoxantrone (MTZ) 8 mg/m2 on days 1, 2, and 3, both plus cytarabine (Ara-C) 100 mg/m2 on days 1 to 7. Following complete remission (CR), patients received one additional cycle of DNR or MTZ chemotherapy and were then eligible for a second randomization between eight cycles of low-dose (LD)-Ara-C 10 mg/m2 subcutaneously every 12 hours for 1 2 days every 6 weeks or no further treatment. RESULTS: A total of 242 patients was randomized to DNR and 247 to MTZ. Median age of both study groups was 68 years. Secondary AML was documented in 26% and 25% of patients in either arm. The probability of attaining CR was greater (P = .069) with MTZ (47%) than with DNR (38%). Median duration of neutropenia was 19 (DNR) and 22 days (MTZ). The greater response rate to MTZ therapy correlated with reduced occurrence of chemotherapy resistance (32% v 47%, P = .001). With a median follow-up of 6 years, 5-year disease-free survival (DFS) is 8% in each arm. Overall survival estimates are not different between the groups (6% v 9% at 5 yrs). Poor performance status at diagnosis, high WBC count, older age, secondary AML, and presence of cytogenetic abnormalities all had an adverse impact on survival. Secondary AML and abnormal cytogenetics predicted for shorter duration of CR. Among complete responders, 74 assessable patients were assigned to Ara-C and 73 to no further therapy. Actuarial DFS was significantly longer (P = .006) for Ara-C-treated (13% [SE = 4.0%] at 5 years) versus nontreated patients (7% [SE = 3%]), but overall survival was similar (P = .29): 18% (SE = 4.6%) versus 15% (SE = 4.3%). Meta-analysis on the value of Ara-C postremission therapy confirms these results. CONCLUSION: In previously untreated elderly patients with AML, MTZ induction therapy produces a slightly better CR rate than does a DNR-containing regimen, but it has no significant effect on remission duration and survival. Ara-C in maintenance may prolong DFS, but it did not improve survival.

Acute Disease↗
PubMed1997

Non-specifically labelled cells that simulate bone marrow metastases in patients with non-metastatic breast cancer.

AIMS: To determine whether the presence of disseminated bone marrow tumour cells at diagnosis is a prognostic factor for breast cancer patients at high risk of recurrence or bone metastasis, and to assess their presence as a criterion for evaluation of the potential benefits of adjuvant chemotherapy. METHODS: Multiple bone marrow aspirates from 72 breast cancer patients free from metastasis were obtained during surgery at the time of diagnosis and were tested immunologically by alkaline phosphatase antialkaline phosphatase technique with a panel of three antiepithelial monoclonal antibodies (MoAb) KL1, EMA, and HMFG2. RESULTS: In nine of 72 patients, with each MoAb tested, numerous strongly positive cells always isolated were observed. However, it was demonstrated that these cells were non-specifically labelled and could be found in normal controls. CONCLUSIONS: There was no evidence of marrow tumour cells in 72 operable breast cancer patients. It is suggested that published results may be greatly overestimated and that non-specific labelling may be undetected. More specific MoAb should be found and a correlation with molecular biology should be performed if this criterion is to be considered as a prognostic factor.

Adult↗
PubMed1997

N-Myc gene amplification is a major prognostic factor in localized neuroblastoma: results of the French NBL 90 study. Neuroblastoma Study Group of the Société Francaise d'Oncologie Pédiatrique.

PURPOSE: To assess the relevance of N-Myc gene amplification (NMA) as a prognostic factor in localized neuroblastoma (NB) and to evaluate whether less intensive adjuvant treatment is advisable in infants without NMA. PATIENTS AND METHODS: Assessment of NBs included clinical and imaging data to allow tumor-node-metastasis (TNM) staging, biologic determinations (N-Myc gene analysis), and standard histology and work-up to eliminate metastatic spread (metaiodobenzylguanidine [MIBG] scintigraphy and extensive bone marrow staging). Resectability was defined according to imaging findings. Chemotherapy was indicated in children older than 1 year at diagnosis who had postoperative residual disease or lymph node (LN) involvement, in infants with NMA, or as primary treatment in children with an unresectable NB, including dumbbell tumors. Radiotherapy was recommended in children older than 1 who presented with persistent gross residual disease at the end of therapy. RESULTS: Between 1990 and 1994, 316 consecutive children who presented with a localized NB were registered in the NBL 90 study. The median age was 12 months, and 42 patients had dumbbell tumors (13%). NMA was found in 22 of 225 assessable children (10%) and correlated with adverse prognostic indicators such as age older than 1 year, an abdominal primary tumor, a large tumor (T3), and unresectability. Among 186 children who had primary excision, five died of surgery-related complications. Primary chemotherapy was given to 130 patients, which allowed removal of the tumor in all but four. The 5-year overall survival (OS) and event-free survival (EFS) rates were, respectively, 91% and 84% with a median follow-up time of 36 months. The outcome of infants and older children was similar (P = .2). EFS of patients with resectable tumors was slightly better than with unresectable primary tumors (EFS, 89% v 78%; P = .02). In dumbbell NBs, neurologic recovery was achieved in 74% of cases that presented with symptoms, and initial laminectomy was avoided in 75% of children. In a univariate analysis, large tumors, high neuron-specific enolase (NSE) and lactate dehydrogenase (LDH) levels, positive LNs, macroscopic residue, and NMA adversely influenced outcome. In the multivariate analysis, NMA was the most powerful unfavorable predictive indicator: OS and EFS rates for these children were 36% and 32%, compared with 98% and 90% in nonamplified tumors (P < .001). CONCLUSION: Our data confirm the overall good prognosis of localized NBs, even when unresectable. NMA is the most relevant adverse prognostic factor in localized NBs, and more intensive treatment should be investigated in these patients. Prospective studies of other biologic factors are warranted to tailor therapy more accurately. The EFS of children who underwent primary surgery was excellent, and further justifies elimination of adjuvant treatment provided they have no NMA. Despite the elimination of postoperative therapy, infants with non-NMA tumors have an excellent outcome, which suggests that initial chemotherapy can be further reduced in case of unresectable NBs.

Adolescent↗
PubMed1997

Systemic effect of intrathecal methotrexate during the initial phase of treatment of childhood acute lymphoblastic leukemia. The European Organization for Research and Treatment of Cancer Children's Leukemia Cooperative Group.

PURPOSE: The in vivo response to prephase corticosteroid therapy for 1 week has been described as a major prognostic factor in childhood acute lymphoblastic leukemia (ALL). Patients with less than 1,000 blasts/microL at day 8 are considered responders and have a better prognosis. This prephase therapy is usually considered as an evaluation of glucocorticoid sensitivity. In fact, it also includes one intrathecal (IT) injection of methotrexate (MTX). In this study, we try to clarify the influence of this injection of IT MTX on the response to the prephase therapy. PATIENTS AND METHODS: This retrospective study analyzed the response to prephase therapy in 1,044 children with ALL entered onto the European Organization for Research and Treatment of Cancer (EORTC) trial 58881 of the Children's Leukemia Cooperative Group (CLCG). Analysis was restricted to 732 cases with an initial blast count greater than 1,000/microL. The following variables were tested to analyze response to prephase therapy: age, sex, evaluated risk factor (RF), blast count on day 0, actual dose of prednisolone administered, immunophenotype (T v non-T), and day of IT MTX. For statistical analysis, the variable day of IT MTX (D) was stratified into three groups: group 1 if D less than 2, group 2 if D > or = 2 but < or = 6, and group 3 if D greater than 6. RESULTS: All variables tested had a significant influence on response to the prephase therapy. This was especially true for IT MTX: 90.4% responders in group 1, 76.9% in group 2, and 70% in group 3 (P < .001). Immunophenotype was also a major predictor of response to the prephase: 88% responders in B-lineage ALL versus 56.2% in T-lineage ALL. IT MTX had a significant influence in B-lineage ALL (96% responders in group 1, 90% in group 2, and 79% in group 3; P < .001), whereas the influence could not be detected in T-lineage ALL. CONCLUSION: These results clearly demonstrate a therapeutic systemic effect of low doses of IT MTX in childhood ALL, and response to prephase therapy should not be considered as an in vivo test for cortico-sensitivity only. Earlier use of IT MTX leads to a higher percentage of responders.

Antimetabolites, Antineoplastic↗
PubMed1997

Treatment of mantle-cell lymphomas with the VAD +/- chlorambucil regimen with or without subsequent high-dose therapy and peripheral blood stem-cell transplantation.

BACKGROUND: MCL is a well-described clinicobiological entity that presents the worst prognosis of the small-cell lymphomas. No treatment is known as the reference treatment. On the basis, first, of clinicobiological similarities between MCLs and multiple myelomas and, second, of our experience of chlorambucil in high intermittent dose in MCLs, we have treated MCL with the VAD regimen both with and without chlorambucil. PATIENTS AND METHODS: Thirty disseminated MCL patients from three institutions, most in relapse (70%), were treated with the classical VAD regimen: 4 weeks VAD for 12 patients and VAD with 12 mg chlorambucil (d20-d29) for 5 weeks (VAD+C) for 18 patients. Five patients received complementary high-dose therapy (Alkeran or cyclophosphamide HD with TBI) and peripheral blood stem-cell transplantation. RESULTS: Complete response was achieved in 43% of the patients in which 84.5% were treated by VAD+C. The median overall survival from the diagnosis was 52 months, and from the first VAD +/- C (OSvad) was 22.5 months, with a 20.5 month (0-75) median follow-up between diagnosis and the first VAD +/- C. The OSvad was significantly better for patients with fewer than two prognostic factors (ECOG, lymphocytosis, blastic variant, LDH level, and Ki-67 score). Four of five patients treated with HDT and PBSCT were alive in CR 12.5 months (7-22) after the first VAD +/- C regimen. CONCLUSION: The VAD regimen appears effective in disseminated MCL patients and even better when associated with chlorambucil. HDT and PBSCT appear promising in younger patients in CR before HDT. A multicenter prospective study is in preparation to confirm these encouraging results.

Aged↗
PubMed1996

Urinary excretion of methylated catecholamine metabolites in a child with neuroblastoma maturing into ganglioneuroma.

Neuroblastomas are malignant tumors derived embryonically from the neural crest. Biological diagnosis relies on assay of urinary excretion of homovanillic acid (HVA), vanillylmandelic acid (VMA), and dopamine (DA). Spontaneous regression of these neoplasms has been reported by numerous investigators. The authors report the case of a child with neuroblastoma that illustrates the relationship between catecholamine metabolites and tumor maturation. At 1 month of age, this infant presented an adrenal neuroblastoma with multiple metastases (stage IV); the initial histological diagnosis based on examination of cutaneous metastases was neuroblastoma. At the age of 6 months, after chemotherapy, the primary tumor was resected; hepatic metastases were discovered at laparotomy. The histological diagnosis for all lesions was highly differentiated, mature ganglioneuroma-like tissue. The main biochemical abnormality at the time of diagnosis was an elevation in normetanephrine (NMN). HVA was only slightly increased but rose progressively during chemotherapy; it dropped back to normal levels after the sixth course. This case illustrates the potential benefits of separate assays of urinary methylated catecholamine metabolites for biochemical diagnosis and therapeutic management of neuroblastoma in addition to assays of HVA, VMA, and DA. Case findings suggest existence of a transformation process with maturation of the tumor involving enzymatic regulation and expression of MAO.

Adrenal Gland Neoplasms↗
PubMed1996

Loss of heterozygosity of the RB gene is a poor prognostic factor in patients with osteosarcoma.

PURPOSE: The usual therapy of osteosarcoma is neoadjuvant chemotherapy, followed by surgery, then by postoperative chemotherapy. There is no prognostic factor to predict, at diagnosis, the histologic response and final outcome. Inactivation of the retinoblastoma-susceptibility gene RB is associated with the pathogenesis of several human cancers. In primary osteosarcomas, loss of heterozygosity (LOH) at the RB locus has been found in greater than 60% of cases. The aim of this study was to determine the potential early prognostic value of LOH of RB gene on the biopsy material at diagnosis. PATIENTS AND METHODS: Forty-seven patients with primary osteosarcoma, treated in four French institutions, were studied. LOH was studied by polymerase chain reaction (PCR) of an informative RB DNA polymorphism. RESULTS: Assessment of LOH at the RB gene could be completed on 34 heterozygous patients only. LOH was found in 24 cases (70%). The event-free survival (EFS) rate at 60 months is 100% for patients without LOH, 43% for all patients with RB LOH, and 65% for nonmetastatic patients with RB LOH. The difference in EFS is highly significant at P = .008 and P = .024, respectively. Histologic response after preoperative chemotherapy did not show significant correlation with LOH status. CONCLUSION: RB gene LOH appears to be an early predictive feature for osteosarcomas that indicates a potential unfavorable outcome. RB LOH study might shortly help to identify high-risk patients earlier. If this is verified, therapy could then be adapted earlier to the individual's real risk of relapse.

Adolescent↗
PubMed1995

Primary bronchogenic squamous cell carcinoma in children: report of a case and review of the literature.

The authors report a case of primary bronchogenic squamous cell carcinoma (SCC) revealed by recurrent pneumonia in an 11-year-old boy. Four years after complete surgical resection followed by external radiotherapy, the patient is currently relapse- and metastasis-free. To our knowledge, this is only the sixth pediatric case of primary bronchogenic SCC reported to date.

Carcinoma, Squamous Cell↗
PubMed1995

Thyroid spindle epithelial tumor with thymus-like differentiation (the "SETTLE" tumor). An immunohistochemical and electron microscopic study.

An intrathyroid primary epithelial spindle-cell tumor with mucous cysts is described in a 9-year-old child. Histologically, this well-circumscribed tumor exhibited a nodular pattern, a prominent spindle cell component with minimal pleomorphism, and well-differentiated mucinous glands within fibrous bands. The spindle cells demonstrated diffuse immunopositivity for cytokeratin and vimentin. Electron microscopy of tissue sections demonstrated that cells contained bundles of cytoplasmic tonofilaments and numerous desmosomes. The light and electron microscopic features and immunohistochemical profile of this tumor were similar to those of recently described thyroid tumors that have been called "SETTLE" tumors (i.e., spindle epithelial tumor with thymus-like differentiation). These uncommon tumors can be considered intrathyroid thymoblastomas and must be regarded as potentially malignant lesions.

Child↗
PubMed1995

Chemotherapy combined with zidovudine and GM-CSF in human immunodeficiency virus-related non-Hodgkin's lymphoma.

OBJECTIVE: The treatment of patients with non-Hodgkin's lymphoma related to the human immunodeficiency virus (HIV-NHL) is complicated by the underlying acquired immunodeficiency syndrome (AIDS). Patients without adverse prognostic factors (no AIDS prior to lymphoma, CD4+ lymphocyte counts greater than 100 x 10(6)/l and good performance status) can be cured of lymphoma and experience long-term survival. Our previous study with the intensive chemotherapy LNH84 regimen yielded a 63% complete response (CR) rate but median survival was only nine months, half of the patients died of AIDS and the other half of their lymphoma. We report here the results of a phase II study combining the same chemotherapy with zidovudine and GM-CSF. Our goal was to improve the treatment outcome over that of our previous study; GM-CSF was expected to decrease the hematological toxicity of chemotherapy and thus permit a dose intensity increase, while zidovudine was supposed to slow down the evolution of AIDS. DESIGN AND SETTING: A phase II non-randomized prospective clinical trial in 7 centres. PATIENTS AND METHODS: Thirty-two consecutive adult patients presenting HIV-NHL and performance status of less than three without active opportunistic infection underwent three cycles of doxorubicin 75 mg/m2, cyclophosphamide 1,200 mg/m2, vindesine 2 mg/m2 for two days, bleomycin 10 mg for two days and prednisolone 60 mg/m2 for five days (ACVB). Chemotherapy was associated with zidovudine (5 mg/kg/d) and GM-CSF (5 mu g/kg/d). The induction phase was followed by a four-month consolidation phase. RESULTS: CR and PR > 75% were observed in 56% of patients; 25% of the patients died during the induction phase. These results were analogous to those of the previous study (63% and 14%, respectively). Neither hematological tolerance nor dose intensity were improved. With a mean follow-up of 23.5 months, median survival was 6.7 months. The rate of non-NHL AIDS-related death during CR was not reduced (22% in our study vs. 16% in our previous one). CONCLUSIONS: GM-CSF failed to reduce significantly the cumulative hematological toxicity of chemotherapy and zidovudine. New antiviral agents without hematological toxicity would perhaps be useful in this setting.

Adolescent↗
PubMed1995

Efficacy of lenograstim on hematologic tolerance to MAID chemotherapy in patients with advanced soft tissue sarcoma and consequences on treatment dose-intensity.

PURPOSE: This two-arm, double-blind, randomized trial was conducted to determine the effects of lenograstim, a glycosylated recombinant human granulocyte colony-stimulating factor (rHu-G-CSF), on the hematologic tolerance of patients with sarcoma treated with mesna, doxorubicin, ifosfamide, and doxorubicin (MAID) chemotherapy. PATIENTS AND METHODS: Forty-eight patients with metastatic or locally advanced soft tissue sarcoma were, following the first cycle of a combination with doxorubicin 60 mg/m2, ifosfamide 7.5 g/m2, and dacarbazine 900 mg/m2, ifosfamide 7.5 g/m2, and dacarbazine 900 mg/m2 given on days 1 to 3, randomized to receive either lenograstim 5 micrograms/kg/d by once-daily injection from day 4 to day 13, or its vehicle. For subsequent cycles, 28 patients continued on the same chemotherapy and lenograstim was systematically given as prophylactic treatment in an open manner. RESULTS: Following the first cycle of MAID, the duration of neutropenia was reduced in patients who received lenograstim as compared with those who received placebo, with a median duration of neutropenia ( < 0.5 x 10(9)/L neutrophils) of 0 days (range, 0 to 3) and 5 days (range, 0 to 10), respectively (P < .001). All patients who received lenograstim had recovered at least 1 x 10(9)/L neutrophils (polymorphonuclear lymphocytes [PMN]) on day 14, compared with only one of 26 in the placebo group (P < .001). The median time to recover this neutrophil level was 12 days (range, 10 to 13) and 17 days (range, 14 to 21), respectively (P < .001). Neutropenic fever occurred in five (23%) and 15 (58%) patients respectively (P = .02). Twenty-eight patients received at least two cycles (median, four) of MAID at the same dose. Toxicity remained constant across all treatment cycles. A progressive increase in thrombocytopenia was noted, with median platelet nadirs of 102 x 10(9)/L at cycle 2 and 19.5 x 10(9)/L at cycle 6, but did not result in significant treatment modifications. Consequently, median relative dose-intensities remained greater than 0.95 for up to six consecutive MAID cycles. CONCLUSION: Lenograstim significantly improved hematologic tolerance in patients treated with the MAID chemotherapy regimen and, therefore, allowed optimal adhesion to the theoretic doses planned for up to six cycles. Whether such an optimization in relative dose-intensity will result in an improvement of treatment efficacy remains to be determined.

Adult↗
PubMed1995

Phase II trial of cisplatin, fluorouracil, and pure folinic acid for locally advanced head and neck cancer: a pharmacokinetic and clinical survey.

PURPOSE: To analyze clinical and pharmacokinetic data of cisplatin (CP)/fluorouracil (FU)/l folinic acid (l FA) chemotherapy administered as first-line treatment to locally advanced head and neck cancer patients. PATIENTS AND METHODS: Thirty-nine patients (35 men and four women; median age, 60 years; six stage III and 33 stage IV) received CP on day 1 (100 mg/m2) followed by l FA (200 mg/m2/d x 5) plus FU (500 mg/m2/d x 5) administered by continuous venous infusion (three cycles planned). Mean plasma concentrations of FU, l FA, and 5-methyltetrahydrofolate (5MTHF) over the cycle were computed. RESULTS: Clinical response was assessable for 33 patients. Response rates on the primary tumor site (n = 33) were 63.7% complete responses (CRs), 24.2% partial responses (PRs), and 12.1% treatment failures. Response rates on lymph nodes (n = 27) were 40.7% CRs, 37.1% PRs, and 22.2% treatment failures. The most frequent toxicity was mucositis (36.2% of cycles grade 3 to 4). Grade 3 to 4 nausea-vomiting, diarrhea, neutropenia, and thrombocytopenia occurred in 6.7%, 1.9%, 13.3%, and 1% of cycles, respectively. Pharmacokinetic analysis showed a wide interpatient variability for both FU (mean, 1.01 mumol/L; range, 0.16 to 2.09), l FA (mean, 1.89, mumol/L; range, 0.52 to 7.88) and 5MTHF plasma concentrations (mean, 3.85 mumol/L; range, 1.30 to 8.11). A significant correlation was demonstrated between FU concentration and hematologic toxicity grade, mucositis grade, and nausea-vomiting/diarrhea grade. Regarding tumor response, patients who failed to respond significantly exhibited lower FU and total folate concentrations than patients with a CR or PR. CONCLUSION: This study highlights the efficacy of CP/FU/l FA in head and neck carcinoma and establishes the clinical importance of coupled FU/FA pharmacokinetics to predict pharmacodynamic variability.

Adult↗
PubMed1995

Response to fluorouracil therapy in cancer patients: the role of tumoral dihydropyrimidine dehydrogenase activity.

PURPOSE: The aim of the present study was to analyze the role of thymidylate synthase (TS; main cellular target of fluorouracil [FU]) and dihydropyrimidine dehydrogenase (DPD; rate-limiting enzyme of FU catabolism) in tumoral biopsies with respect to FU responsiveness. PATIENTS AND METHODS: This prospective study was conducted on 62 head and neck cancer patients (six stage II, 16 stage III, and 40 stage IV). All received first-line chemotherapy with biomodulated FU (5-day continuous infusion). Before treatment, a tumor biopsy and control biopsy (symmetrical nontumoral area) were obtained. Cytosolic TS and DPD activities were measured using radioenzymatic assays. RESULTS: DPD activity was detectable in all samples, without a significant difference between tumoral (median, 60 pmol/min/mg protein; range, 13 to 193) and nontumoral samples (median, 68 pmol/min/mg protein; range, 12 to 150). Tumoral TS and tumoral DPD were not significantly influenced by tumor localization or tumor staging. Among 52 tumors assessable for clinical response, we observed 46% complete responses (CRs), 33% partial responses (PRs), and 21% no responses (NRs). No relationship was demonstrated between TS activity and response to FU therapy. The comparison of tumoral DPD between complete responders and partial or nonresponders showed a trend toward significance (P = .06). In an attempt to reduce variability, we analyzed the tumoral/nontumoral DPD activity ratio; complete responders exhibited a significantly lower normalized DPD than partial or nonresponding patients (median, 0.86, 1.18, and 1.42 for CR, PR, and NR, respectively; CR v PR plus NR, P = .03). CONCLUSION: Although resistance to FU is multifactorial, the present clinical study suggests that FU catabolism in target cells is probably a determinant factor for FU responsiveness in cancer patients and justifies the clinical use of specific DPD inhibitors as FU biomodulators.

Adult↗
PubMed1995

Preirradiation chemotherapy including "eight drugs in 1 day" regimen and high-dose methotrexate in childhood medulloblastoma: results of the M7 French Cooperative Study.

The aim of this study was to evaluate the feasibility and efficacy of a protocol that includes "sandwich" chemotherapy, that is, chemotherapy alternated with radiotherapy, and reduced doses of supratentorial irradiation in children with medulloblastoma. Between March 1985 and September 1988, 70 successive children with newly diagnosed medulloblastoma from eight centers were treated in this prospective nonrandomized study. Patients were assigned to two risk groups. Group A included patients with macroscopically complete or subtotal excision, no brainstem involvement, no atypical cells in the cerebrospinal fluid, normal myelography, and who were more than 2 years of age. Group B patients encompassed those who did not fit the criteria for Group A. Two children were excluded from analysis after histological review confirmed ependymoma. Thus, a population of 68 children was selected, with 31 in Group A and 37 in Group B. Treatment consisted of two courses of the "eight drugs in 1 day" ("8/1") regimen followed by two courses of high-dose methotrexate (12 g/m2). Radiotherapy was begun during the 7th week after surgery in Group A and during the 5th week in Group B. In patients older than 2 years, the median radiation dose to the posterior fossa, the spinal axis, and the brain was 54 Gy, 36 Gy, and 27 Gy, respectively. Group B patients received postirradiation chemotherapy with four 8/1 courses monthly. The median time from surgery to radiation therapy was 50 days (range 21 to 141 days). One fatality due to chicken pox on Day 102 and one World Health Organization Grade IV infection occurred. The estimated 5- and 7-year disease-free survival (DFS) rates were 62% and 59%, respectively. These were 74% and 62% in Group A and 57% and 57% in Group B. Patient age, extent of resection, and radiation dose to the whole brain had no prognostic value. Patients with metastasis had a nonsignificant trend for a worse prognosis than patients with nonmetastatic disease (7-year DFS 45% vs. 68%, p = 0.11). In Group B, the 7-year DFS rates for children who received more or less than 30 Gy to the brain were 69% and 52% respectively (p = 0.15). There were recurrences in the posterior fossa (37%), spine (20%), and brain (20%). After a review of radiotherapeutic treatments, only one supratentorial failure could be blamed on reduction of the supratentorial radiation dose. This "sandwich" chemotherapy appeared to be feasible and did not show adverse survival data when compared to other series.

Adolescent↗
PubMed1995

[Vertebral osteosarcoma. Review of the literature apropos of a case].

Osteosarcoma of the vertebral column (OSV) is a rare tumor which represents 0.85% to 2% of all osteosarcomas. In 95% of the cases they manifest themselves through pains and 80% of other cases through neurological disorders. Usually located on lumbar vertebrae it can also be found on the rest of the vertebral column. Its radiologic aspect is one of lysis in 48% of cases but a condensation can also be met in 27% of cases. The differential diagnosis with an osteoblastoma is difficult and must be left in the hands of the pathologist who bases it on precise criteria (cellular pleomorphism, stroma, presence of giant cells...). The secondary osteosarcoma of the vertebral column represents 30% of all cases of OSV. The heterogeneity of the studies has made it difficult to quantify them. The prognosis of OSV is poor: survival average is of 15.3 months and relative risk of recurrence compared to a femoral lesion is of 3.9 months.

Adolescent↗