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Biomedical subjects

G Deb

Publications and source records attributed to G Deb.

At least 19 recordsLinked to original sources
PubMed2004

Ifosfamide/carboplatin/etoposide (ICE) as front-line, topotecan/cyclophosphamide as second-line and oral temozolomide as third-line treatment for advanced neuroblastoma over one year of age.

Children affected by advanced neuroblastoma have a discouraging prognosis, but intensive induction chemotherapy may increase the complete response rate. The combination of ifosfamide, carboplatin and etoposide (ICE) was used for the first time as front-line regimen in patients with stage 4 neuroblastoma over the age of 1 y. Similarly, second-line treatment for children with relapsed neuroblastoma, particularly after high-dose chemotherapy, has been unsatisfactory. The combination of topotecan and cyclophosphamide was studied in resistant or relapsed solid tumors. Furthermore, there is a need for effective palliative treatment in patients failing therapy. Temozolomide, a new dacarbazine analog with optimal oral bioavailability, is being used in an ongoing phase II study as an alternative to oral etoposide. Seventeen patients with stage 4 neuroblastoma have entered the ICE study; 15/16 (94%) major responses after induction were observed and 6/16 (37%) evaluable patients are disease free after a median of 51 mo. Twenty-one patients with relapsed/refractory disease (of whom 13 neuroblastomas) entered the topotecan/cyclophosphamide study: 7/21 (33%) patients responded. Forty-one patients entered the temozolomide study (of whom 16 had neuroblastomas): stable disease and symptom relief were obtained in 15/30 (50%) evaluable patients. Intensive induction with ICE resulted in a faster response with high response rate; a larger study with longer follow-up is needed to confirm a survival advantage. Second-line treatment was effective in obtaining remissions, some of them long lasting. Third-line treatment did not elicit measurable responses in neuroblastoma, but achieved prolonged freedom from disease progression and excellent palliation in several patients.

Adolescent↗
PubMed1997

The response of parotid hemangiomas to the use of systemic interferon alfa-2a or corticosteroids.

OBJECTIVE: To evaluate medical treatment for hemangiomas involving the parotid area with or without other areas of involvement. DESIGN: Retrospective analysis of pediatric patients treated medically for proliferative hemangiomas of the parotid region with or without hemangiomas in other regions. Indications for treatment included respiratory symptoms relating to hemangiomas of the upper airway, difficulty feeding, rapid rate of growth of the hemangioma, and deformity or obstruction of the ear canal. SETTING: New York University Multidisciplinary Vascular Anomaly Conference, New York, NY, and the Pediatric Oncology Department of Ospedale Pediatrico Bambino Gesu, Rome, Italy. PATIENTS: Thirteen patients with proliferative hemangiomas in the parotid area were treated medically to inhibit growth and enhance involution of the hemangioma. INTERVENTION: Six patients were treated with corticosteroids alone (2-4 mg/kg daily). Two patients were treated with corticosteroids (2-4 mg/kg daily) followed by interferon alfa-2a (3 million U/m2 daily) because of a failure to respond to corticosteroid therapy. One patient was treated with interferon alfa-2a alone (3 million U/m2 daily). Four patients were initially treated with interferon alfa-2a, then treated with corticosteroids. One of these patients required intralesional corticosteroid therapy for a massively enlarged lip and is therefore included in this group. The other patient was given oral corticosteroids for unknown reasons at another institution. In the remaining 2 patients, there was no response to the use of interferon alfa-2a. MAIN OUTCOME MEASURES: The size, bulk, and symptoms relating to the hemangiomas of the patients were assessed. RESULTS: None of the patients had a significant improvement of the lesions of the parotid hemangiomas. In contrast, for those patients with clinical symptoms due to hemangiomas elsewhere or with cutaneous involvement typical of hemangiomas, the symptoms improved with either of the above therapies, and the cutaneous areas demonstrated signs of involution. CONCLUSIONS: The results in the 13 patients in this article demonstrate that hemangiomas in certain anatomic sites, such as the parotid area, may be more resistant to therapy with corticosteroids or interferon alfa-2a. Differences in drug metabolism, caliber of blood vessels, and/or blood flow in the parotid gland may account for this observation.

Antineoplastic Agents↗
PubMed1997

Spindle cell (Kaposiform) hemangioendothelioma with Kasabach-Merritt syndrome in an infant: successful treatment with alpha-2A interferon.

A two-month-old infant developed a vascular tumor of the right flank which upon biopsy proved to be a spindle cell hemangioendothelioma. The increased capillary bed characterizing the neoplasm caused a severe thrombocytopenia together with a consumption coagulopathy (Kasabach-Merritt syndrome). The patient, who was dependent on platelet transfusions, improved quickly after interferon alpha-2a was given at the dosage of 3,000,000 U/m2, with resolution of the Kasabach-Merritt syndrome after three weeks and a 75% decrease of the tumor volume within three months of treatment.

Antineoplastic Agents↗
PubMed1996

Role of deferoxamine in tumor therapy.

Several studies are consistent with the hypothesis that available iron may have some role in promoting tumor cell growth with different biological mechanisms. For this reason, several studies have been carried out to demonstrate the antitumor activity of deferoxamine (DFO), an iron chelator with a high affinity for ferritin-bound iron. In particular, the effects of DFO have been studied in patients with neuroblastoma, where ferritin is in part tumor derived and high concentrations correlate with poor outcome. To date, in vitro and in vivo studies demonstrating the antitumor effects of DFO are very promising, but further investigations are required to establish an exact role for DFO in the treatment of cancer.

Antineoplastic Agents↗
PubMed1996

Sporadic acute lymphocytic leukemia arising in a patient with neurofibromatosis and xanthogranulomatosis.

We present a case report of a child who developed acute lymphoblastic leukemia, neurofibromatosis, optic glioma, and xanthogranulomatosis. This complex is unusual, not previously described, and appears to be a coincidence of different diseases. The importance of this case is that it may offer a clue to the genetic base of neurofibrosis syndromes including leukemic associations.

Glioma↗
PubMed1995

Deferoxamine followed by cyclophosphamide, etoposide, carboplatin, thiotepa, induction regimen in advanced neuroblastoma: preliminary results. Italian Neuroblastoma Cooperative Group.

Based upon phase I and II studies of deferoxamine alone and in combination with cytotoxic agents cyclophosphamide, etoposide, carboplatin, and thiotepa (D-CECaT), we initiated a single arm multicentre trial in 1992 for advanced neuroblastoma. 57 of 65 patients who entered the trial were evaluable. Following 4 courses of the D-CECaT, almost all the patients underwent surgery. Toxicity was moderate and mainly reversible myelosuppression. The post-surgically defined responses in stage 3 high risk, stage 4 moderate risk and stage 4 high risk patients included 24 complete responses, 26 partial responses, and 3 minor responses, and 4 patients had progressive disease. These patients are being followed to determine the impact of this programme on their overall survival.

Adolescent↗
PubMed1995

[123I]MIBG scintigraphy in neuroblastoma: a comparison between planar and SPECT imaging.

The aim of the present study was to assess the utility of SPECT imaging with [123I]MIBG in patients with neuroblastoma (NB). Twenty-two children were studied (11 males and 11 females: age range: newborn to 11 years). A total of 39 studies were performed in different clinical phases. Both planar (at 24 and occasionally 48 hours) and SPECT (at 24 hours) imaging were performed in all cases. Planar studies gave a sensitivity of 87.5% (evidence of the disease in 21 of 24 studies performed in children with known NB lesions) and a specificity of 93.3% (true negative results in 14 of 15 studies performed in disease-free patients). In the same patients SPECT gave a sensitivity of 95.8% (23 of 24 positive studies and a specificity equal to that of planar scanning. In 5 of 21 studies positive at planar scanning SPECT showed 9 additional lesions. In conclusion, [123I]MIBG SPECT imaging compared to planar scanning can demonstrate a greater number of lesions. Its use seems to be indicated mainly in cases in which diagnostic assessment is difficult, such as small residual tumors or in the follow up of children no longer in therapy, in whom it can lead to an early diagnosis of relapse.

3-Iodobenzylguanidine↗
PubMed1993

D-CECaT: a breakthrough for patients with neuroblastoma.

In view of the high relapse rate following chemotherapy for patients with advanced neuroblastoma (NB) and primitive neuroectodermal tumors (PNET), we designed a novel chemotherapy program which incorporated the iron chelator deferoxamine. The purpose of the deferoxamine was to sensitize the cells to standard chemotherapy. The D-CECaT regimen contained (in mg/m2): deferoxamine 4500 during days 1-5; cyclophosphamide 600 mg over days 6 and 7; etoposide 300 mg over days 7 and 8; carboplatin 100 mg over days 7 and 8; and thiotepa 30 mg over days 6-8. Between October 1989 and May 1992 we entered 23 advanced NB and two PNET patients. Sepsis occurred in four courses, nausea and vomiting in 30 courses, and 50 courses required blood and platelets. Responses observed in previously untreated patients with stage III NB: six out of six CR (17+ to 41+ months), with stage IV NB, nine out of 11 CR (14+ to 28+ months), two out of 11 VGPR (22+ months), with stage IV PNET two out of two CR (1+ to 35+ months). With previously treated and failed stage IV NG, two out of six VGPR for 19+ and 20 months, and four out of six PR 1, 8, 9 and 11 months. Median survival for 19 new patients was 22+ months (6 to 41+ months; two patients in CR died at 7 months during adjuvant autologous marrow transplant). In conclusion, D-CECaT is an effective initial cytoreductive regimen for advanced stage NB/PNET patients. Additional patients and studies are required to determine its use as an alternative to autologous bone marrow transplantation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Deferoxamine, cyclophosphamide, etoposide, carboplatin, and thiotepa (D-CECaT): a new cytoreductive chelation-chemotherapy regimen in patients with advanced neuroblastoma.

Thirteen patients with Stage III (3 patients) or Stage IV (10 patients) neuroblastoma were treated with a new iron chelation-cytotoxic therapy regimen. Deferoxamine given for five consecutive days followed by 3 days of cyclophosphamide, etoposide, carboplatin, and thiotepa (D-CECaT) caused moderate to severe myelotoxicity. In 39 courses there were four episodes of sepsis; platelet and packed red blood cell transfusions were required in 72% and 82% of courses, respectively. Mild nausea and vomiting occurred in 52% of courses. Objective responses after two courses were observed in 12 of 13 patients. Three of four partial responses were achieved in previously treated relapsed patients, and seven of eight complete responses (four of which were surgically documented) were achieved in previously untreated patients. This cytoreduction regimen appears to be an improvement over other initial induction regimens and may be worth testing in larger populations.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

An improved technique for peripheral blood stem cell collection in small patients.

Peripheral Blood Stem Cell collection in adults is a consolidated method for autografting. The same procedure is less easily performed in pediatric patients due to low weight, vascular access problems and anticoagulant side effects. Great efforts have been made to overcome technical difficulties and make apheresis in children a reliable and safe procedure.

Adolescent↗
PubMed1990

Effects of a single course of deferoxamine in neuroblastoma patients.

A phase II trial of a single 5-day course of deferoxamine in 9 patients with neuroblastomas was completed. Within 2 days of completion of treatment responses were observed in 7 of 9 patients and there was no drug toxicity. These responses were a decrease in bone marrow infiltration and, in one patient, a measurable reduction in her tumor mass. We conclude that deferoxamine given as an 8-h i.v. infusion daily for 5 days at 150 mg/kg/day has antitumor activity.

Adolescent↗
PubMed1990

High-dose carboplatin in combination with etoposide (JET regimen) for childhood brain tumors.

Fourteen patients aged 1 to 15 years with medulloblastoma (six patients), low-grade astrocytoma (four patients), and high-grade astrocytoma (four patients) were treated with carboplatin and etoposide (JET regimen). Six patients had been treated previously, two of them with cisplatin at conventional doses. Carboplatin was administered at 500 mg/m2/day over 5 h on days 1 and 2, in association with pulsed etoposide at 100 mg/m2/day on days 1, 2, and 3. Courses were repeated at 3-week intervals. The disease-specific response rates were as follows: five of six with three complete responses and two partial responses for medulloblastoma; zero of four for low-grade astrocytoma; and two of four with two partial responses for high-grade astrocytoma. Myelosuppression was the main side effect: anemia (hemoglobin less than 8.0 g/dl), thrombocytopenia (less than 25,000/microliter) and leukopenia (less than 1,000 white blood cells/microliters) were noted in 19 of 54, 10 of 54, and 7 of 54 courses, respectively. Gastrointestinal toxicity was very mild, and nephro- and neurotoxicity were not observed. No audiometric abnormalities were demonstrated in seven of seven patients who had not previously received cisplatin, and preexisting audiometric abnormalities were not worsened by the administration of carboplatin in one cisplatin-pretreated patient. The combination of carboplatin and etoposide administered in this study appears to be effective and well tolerated in children with brain tumors. Further studies on a larger number of patients are needed to ascertain its real activity in childhood brain tumors.

Adolescent↗
PubMed1980

Cytokinetic studies in chronic lymphocytic leukemia. Relationship to other variables at diagnosis and survival.

In vitro 3H-thymidine labeling index (LI) of the marrow leukemic cells was determined at diagnosis in 70 patients with chronic lymphocytic leukemia (CLL). Very little labeling of leukemic lymphocytes was observed, median LI resulting as low as 0.05%. The initial LI was unrelated to age, sex, absolute number of circulating lymphocytes, degree of marrow lymphocytosis, clinical staging or survival. We conclude that the initial LI% of the marrow leukemic cells is neither a valid nor practical prognostic factor in patients with CLL.

Adult↗
PubMed1975

Changes in rat adrenal medulla following delta9-tetrahydrocannabinol treatment. A histochemical study.

The effects of acute (10 mg/kg) and chronic 10 mg/kg for 30 days) administration of delta-9-tetrahydrocannabinol (delta9-THC) have been studied histochemically in the rat adrenal medulla, which include total catecholamines, noradrenaline, histometric measurements of adrenal medullary areas, calcium content of the medullary cells along with adenosine triphosphatase (ATPase), acetyl cholinesterase (AChE) and butyryl cholinesterase (BChE) activities. Acute delta9-THC treatment reduced the total catecholamine content (including noradrenaline) of the gland, was accompanied by increased ATP-ase, AChE, BChE activities and increased calcium distribution in the gland. Chronic delta9-THC treatment caused significant hypertrophy of the chromaffin tissue, with decreased total catecholamine content, although noradrenaline containing areas exhibited no notable change. The calcium content and ATPase activity were increased along with a concomitant increase in AChE and BChE activities. Although the changes in adrenal medullary enzyme activities following both acute and chronic delta9-THC treatment are qualitatively similar, marked quantitative increase is noted in the chronically treated groups. The results indicate an increased total catecholamine releasing activity of the adrenal medulla following acute delta9-THC treatment, while chronic delta9-THC administration produces a preferential release of adrenaline.

Acetylcholinesterase↗
PubMedDate not supplied

Peripheral blood stem cells in children with solid tumors. Part I. Feasibility and application.

A method for collecting peripheral blood mononuclear cells following mobilizing chemotherapy in pediatric patients is described. The critical elements of the method included temporary heparinization of the patient to reduce citrate overload, and limiting extracorporeal circulation to 15% of the patient's blood volume using packed red blood cells and albumin. A median of 0.9 x 10(8) mononuclear cells/kg per collection were harvested in 40 collections from eight patients with only one episode of fever and chills. Peripheral blood stem cells were reinfused into six of these patients with refractory/recurrent pediatric tumors after intensive chemotherapy. Bone marrow reconstitution followed with a mean of 30 days (19-38) for absolute neutrophils and 48 days (32-275+) for platelets. Previous chemotherapy did not appear to affect peripheral blood stem cell efficacy in reconstituting chemotherapy-ablated bone marrow.

Adolescent↗