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 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty patients with astrocytomas recurrent after surgery +/- radiation were treated on a phase II protocol of the new anthracycline derivative menogaril 115 mg/m2 administered intravenously once per week. Sixteen patients were evaluable for treatment efficacy. No patient achieved a major therapeutic response. Three patients (19%) had stable disease for greater than 8 weeks, including one who showed minor evidence of tumor regression, but less than 50%. Thirteen patients failed. Treatment was well tolerated. One patient developed granulocytopenia, while none developed thrombocytopenia. Four patients required an interruption in their treatment for one to two weeks because of development of granulocytopenia (one patient) or other reasons. Other toxic effects included arm vein phlebitis and skin irritation, skin discoloration of the infused arm, mild to moderate nausea and vomiting, diarrhea, stomatitis, and a fatal central venous catheter infection. Despite the fact that menogaril appeared to have therapeutic activity against recurrent astrocytomas in our phase I studies, we could not document any activity in this phase II study.
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PMID:Phase II study of weekly intravenous menogaril in the treatment of recurrent astrocytomas in adults. 133 46

The effect of recombinant human interleukin 1 beta (rHuIL-1 beta) on myelosuppression induced by 3-[(4-amino-2-methyl-5-pyrimidynyl)methyl]-1-(2-chloroethyl)-1-nit rosourea hydrochloride (ACNU) was studied. In in vivo study using BALB/c mice, pretreatment with 1 microgram/mouse of rHuIL-1 beta as a single intraperitoneal (i.p.) injection had a significant preventive effect on thrombocytopenia as well as granulocytopenia induced by ACNU at an intravenous dose of 60 mg/kg. Facilitated recovery by rHuIL-1 beta administered seven days after injection of high-dose ACNU was also observed. Experimental combination immunochemotherapy with high-dose ACNU and rHuIL-1 beta was performed in nude mice inoculated with human glioblastoma subcutaneously. The elongation of the survival time of the tumor bearing nude mice was also observed in combined use of high dose ACNU with rHuIL-1 beta. Seven patients with malignant brain tumors received intravenous 2.5-3 mg/kg ACNU. All patients were subcutaneously injected with 2 x 10(4)-U or more rHuIL-1 beta twice a week or daily. The mean nadir of leukocyte, granulocyte, and thrombocyte counts of the 7 patients received 2.5-3 mg/kg ACNU were significantly higher than in matched historical controls. In combination with rHuIL-1 beta, it may be possible to use chemotherapeutic agents at a relatively high dose.
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PMID:Preventive effects of interleukin 1 beta for ACNU-induced myelosuppression in malignant brain tumors: the experimental and preliminary clinical studies. 133 50

We evaluated the effects of WR-2721 on the toxicity and antitumor activity of the combination of 5-fluorouracil (5FU) and carboplatin (CBDCA) in BALB/c and C57B1/6 mice. On a weekly schedule, i.p. injection of 200 mg/kg WR-2721 at 5 min prior to the administration of this combination enabled us to increase the CBDCA dose from a nontoxic level of 45 mg/kg to a normally toxic dose of 60 mg/kg in non-tumor-bearing BALB/c mice while maintaining the 5FU dose at 100 mg/kg. When WR-2721 was given 30 min before this combination, the CBDCA dose could not be increased to 60 mg/kg without producing drug-related deaths. WR-2721 protected against CBDCA- and 5-FU-induced thrombocytopenia but did not prevent leukopenia or anemia in C57B1/6 mice. The antitumor activity of the combination against colon 26 tumors in BALB/c mice was increased by pretreatment with WR-2721, which facilitated elevation of the CBDCA dose to 60 mg/kg in combination with 100 mg/kg 5FU. These results reveal better therapeutic efficacy for the combination of 5FU and CBDCA following pretreatment with WR-2721.
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PMID:Effect of WR-2721 on the toxicity and antitumor activity of the combination of carboplatin and 5-fluorouracil. 133 72

We report 23 cases of lymphoproliferative diseases which occurred among 2,100 patients with kidney or combined kidney+pancreas transplant. Eleven patients developed a severe diffuse disease within the first 3 months post-transplantation; immunoblastic B cells of recipient origin infiltrated the bone-marrow, transplanted organs, liver, spleen, lymph nodes, lungs, and brain; immunoglobulin abnormalities with fever, leuko-thrombocytopenia and liver dysfunction constituted the symptoms; all patients received anti-lymphocyte globulins; 9 patients were also treated with cyclosporin. Three out of 6 tumors analysed were monoclonal. Epstein-Barr virus was present in 3 lesions analysed. Treatment consisted of cessation of immunosuppressive therapy. Nine patients died with lactic acidosis. Five patients had a less severe form. Seven patients had solid tumors involving the tonsils, lungs (2), lymph nodes (2), and bladder, 8 months after transplantation. All patients received cyclosporin; 4 also received anti-lymphocyte globulins and 3 OKT3. Tumor cells were immunoblasts expressing B cells markers at a late stage of B cell differentiation; 4 tumors were monoclonal. C myc was negative. Treatment consisted of cessation of immunosuppressive therapy, antiviral agents, and monoclonal antibodies (mAb): anti-CD21 and anti-CD24 mAb therapy was followed by cure of the lymphoma in 1 patient, by transient remission in a second one and by failure in the third patient. Two patients had a recurrence of the lymphoma and received chemotherapy; 2 patients died of the lymphoma, 1 died of unrelated cause; 4 are alive, 3 of them having a good graft function.
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PMID:[Lymphoproliferative syndromes associated with Epstein-Barr virus in transplantation]. 133 26

From favorable results with 254-S, a new cisplatin analogue, single administration, we have conducted a clinical study to investigate the efficacy of combination of 254-S, ifosfamide and peplomycin, each of which has a different dose limiting factor. A total of 45 patients, including 22 patients with stage III and IV cervical cancer and 23 cases with recurrent cervical cancer, were treated with at least two courses of 254-S (100mg/m2, iv. Day 1), ifosfamide (1,500mg/body, iv. Day 1-5) and peplomycin (5mg/body, im. Day 1-6), and tumor response was evaluated clinically and by CT scanning. The response rate obtained in patients with advanced disease was 81.8% (PR = 17, CR = 1) and that in cases with recurrence was 60.9% (PR = 12, CR = 2). Myelosuppression was the dose limiting factor. In the 121 courses, grade 3 and 4 of leucopenia and thrombocytopenia were observed with an incidence of 44% and 32%, respectively and DIC occurred in 3 cases with poor PS though they recovered after reducing the 254-S dose to 80 mg/m2. The other toxicities were mild except for alopecia. Anaphylaxia was observed in a case at the second administration though the patient recovered in 15 minutes. There was no death. As to prognosis, a significant prolongation of survival period was observed in recurrent cases and 4 cases are alive (NED) after one and a half year. In the advanced cases, until now 3 cases of stage IV have died from the disease. We have concluded that this regimen is effective as a neoadjuvant chemotherapy for advanced cervical cancer and useful for the treatment of recurrent cervical cancer.
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PMID:[Combination chemotherapy with 254-S, ifosfamide and peplomycin for advanced or recurrent cervical cancer]. 137 59

A 53-year-old woman was admitted with fever and general fatigue in December, 1988. A diagnosis of malignant histiocytosis (MH) was made based on her high level of LDH, thrombocytopenia, mild splenomegaly without systemic lymphadenopathy. There was also bone marrow infiltration large atypical cells and erythro-phagocytosis. VEPA therapy resulted in complete remission. Visual disturbance and left lagophthalmos were recognized in March 1990. These signs indicated central nervous system (CNS) relapse which disappeared after intrathecal methotrexate injection. The same symptoms and signs appeared after another, 5 months. Tumor cells were found not only in the central spinal fluid but also in bone marrow. CNS and bone marrow recurrence were treated with intrathecal methotrexate injection VEPA therapy and cranial irradiation. We diagnosed this case as MH, based on the clinical features which did not include systemic lymphadenopathy and laboratory findings although TcR-gamma rearrangement was observed in bone marrow cells. Only one case of CNS infiltration diagnosed when alive has previously been reported in Japan. We report here a very rare case in which by medical treatment CNS infiltrations was improved twice.
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PMID:[Malignant histiocytosis associated with central neurological symptoms and cerebrospinal fluid involvement]. 138 75

Fifty-six untreated patients with inoperable squamous cell carcinoma of the head and neck were treated with carboplatin 70 mg/m2 i.v. daily on days 1-5 and 29-33 in combination with simultaneous conventional radiation up to a target volume dose of 50 Gy. Depending on tumor response and upon recommendation of surgeons, 21 of 56 patients underwent surgery after a radiation dose of 50 Gy and two courses of carboplatin. Patients who showed pCR after surgery received no further radiotherapy. In all other patients radiotherapy was continued using a shrinking field technique up to a target absorbed dose of 70-74 Gy. Combined modality induced 66% complete remission (CR) and an overall response rate of 98%. After completion of the whole treatment program (combined modality +/- surgery) 53 (94%) of the 56 patients were disease free. The median survival for all patients is 25+ months and the percentage of two-year survivors is 53%. Myelosuppression was the most frequent toxicity, but rarely was severe; leukopenia and thrombocytopenia of WHO grade 3 occurred in 21% of the patients. No other toxicities above WHO grade 2 occurred. Nephrotoxicity, neurotoxicity and ototoxicity were not seen. The addition of carboplatin did not increase the rate of surgical complication over that expected for preoperative radiotherapy. Two patients died of pulmonary embolism after surgery. Combined modality with carboplatin and simultaneous radiation is a highly active and well-tolerated regimen for untreated patients with inoperable squamous cell carcinoma of the head and neck.
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PMID:Simultaneous radiotherapy and chemotherapy with carboplatin in inoperable squamous cell carcinoma of the head and neck: a phase II study. 139 86

Twenty-six patients with advanced renal cell carcinoma were treated with suramin administered by continuous infusion, with dosing determined by a nomogram. One patient achieved a partial response and five patients achieved a minor response or had stable disease for > 3 months. Toxicities included an immune-mediated thrombocytopenia in one patient and Staphylococcus sepsis that was not associated with neutropenia in five patients. Pharmacokinetic parameters were determined by the ADAPT II MAP-Bayesian parameter estimation program. Patient data were fit using a two-compartment open model and first-order rate elimination. This showed a wide interpatient variation in time to target level (median, 13.8 days), volume of distribution (median, 15.2 liters/m2), and t1/2-beta (median, 20.6 days). The patients who achieved a partial response, minor response, or stable disease had a slower elimination rate of suramin, compared to patients with progressive disease. Tumor specimens were obtained prior to therapy and were analyzed for the production of five different growth factor-specific RNA transcripts. These included transforming growth factor alpha, acidic fibroblast growth factor, basic fibroblast growth factor, and platelet-derived growth factor types A and B. No difference in the pattern of growth factor expression was seen in tumors of responding and nonresponding patients. Suramin does not have significant antitumor activity in renal cell carcinoma. The wide variability in pharmacokinetics suggests that individual dosing should be used in future trials of suramin for treatment for other malignancies. Pertinent corollary studies of tumor biology and clinical pharmacology should be included whenever possible in clinical trials in patients with renal cell carcinoma.
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PMID:Phase II trial of suramin in patients with advanced renal cell carcinoma: treatment results, pharmacokinetics, and tumor growth factor expression. 139 2

ImuVert, a new biological response modifier, was evaluated for toxicity and potential efficacy in patients with advanced cancer. This agent consists of sized, labile, natural membrane vesicles associated with ribosomes derived from Serratia marcescens. ImuVert induces enhanced in vitro macrophage and natural-killer-cell-mediated cytotoxicity, and has demonstrated antitumor activity in palpable animal tumor systems. A group of 39 patients with a variety of tumors, 25 men, 14 women, with a mean performance status (Karnofsky) of 80% and median age of 57 years were entered into this trial. ImuVert was administered subcutaneously weekly for a minimum of 3 weeks. A total of 183 treatments were evaluated. Flu-like systemic toxicities, including fever, chills, nausea, vomiting, diarrhea and hypotension were observed. Erythema, induration and tenderness developed at the injection sites. Myelosuppression, thrombocytopenia, anaphylaxis, rental and hepatic toxicities did not occur. All symptoms resolved within 24 h. Two patients with nodular lymphoma achieved a partial response and two minor responses were seen in patients with glioblastoma and melanoma. On the basis of ImuVert's biological activity, and tolerable toxicity it warrants further clinical investigation.
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PMID:Phase I trial of ImuVert (natural membrane vesicles associated with ribosomes) in patients with advanced cancer. 139 37

Twelve neonates with sacrococcygeal teratoma (SCT) have been treated at British Columbia Children's Hospital over the past 5 years. Clinically significant coagulopathy developed in four of these neonates and two died, one before surgical intervention could be undertaken. Disseminated intravascular coagulation (DIC) was found in one patient and thrombocytopenia in another on preoperative laboratory studies. Etiology of the coagulopathy is unclear, but appears to be multifactorial. Although several clinical reviews have noted mortalities due to exsanguinating hemorrhage, no study has focused solely on this issue. The diagnosis of SCT in the neonate at high risk for development of coagulopathy is usually made prenatally. Premature labor is often precipitated by associated polyhydramnios and large tumor size. Fetal distress, prematurity, and low birth weight are common. Presence of placentamegaly, hydrops fetalis, and congestive heart failure are ominous prognostic signs. Early identification of patients at increased risk for development of hemorrhagic complications may allow optimization of their management. Cesarean section should minimize trauma to the SCT during delivery. Expeditious resection of the lesion may improve survival.
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PMID:Coagulopathy associated with large sacrococcygeal teratomas. 140 11


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