Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A phase I evaluation of vindesine was carried out in 69 adult patient with advanced malignancies. Two escalating dose schedules were explored: (a) a single dose every 7--14 days, and (b) daily injections X 5--10 days as tolerated. The main toxic effects were myelosuppression, alopecia, paresthesia, asthenia, myalgia, and hyporeflexia. Antitumor activity was seen during this phase I study in patients with leukemia, lymphoma, and testicular neoplasms. Disease oriented phase II trials of 3--4 mg/m2 every 7--14 days or 1.3--2.0 mg/m2/day X 5--7 days every 3 weeks would be appropriate.
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PMID:Phase I trial of vindesine in patients with advanced cancer. 35 86

N, N', N"-Triethylenethiophosphoramide [Thio-TEPA (NSC 6396)] is the third drug to be evaluated for the treatment of meningeal neoplasia. Eleven patients with meningeal leukemia, lymphoma, or ependymoma were treated with intrathecal thio-TEPA in doses from 1 to 10 mg/m2 of body surface area. There was no hematologic toxicity definitely attributable to thio-TEPA, and neurologic toxcity was limited to mild transient paresthesias of the lower extremities during lumbar sac injection in three patients. Two of those experiencing such paresthesias received concentrated drug solutions to decrease the large injected volumes associated with the higher dosages of thio-TEPA. Three patients achieved complete meningeal remission, and five others had a partial response to therapy.
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PMID:Intrathecal N, N', N"-triethylenethiophosphoramide [thio-TEPA (NSC 6396)] in the treatment of malignant meningeal disease: phase I-II study. 82 15

Out of 16 patients, spinal leptomeningeal neoplastic disease was diagnosed by MRI in 4 patients, myelography in 14 patients and CT myelography in 12 cases. MR was superior to myelography in 2 patients, in another 2 patients MRI was equally diagnostic. The cerebrospinal fluid of every patient contained malignant cells. Histological evidence for primary central nervous system tumors was found in 5 cases. In 10 cases, non-neuraxial malignancy consisted of small cell carcinoma of the lung (7 cases), and leukemia and lymphoma (3 patients). In 1 patient, primary leptomeningeal malignant melanoma was confirmed at autopsy. Preferential thoracolumbar neoplastic morphologic manifestation correlated with the presence of conus and cauda equina syndrome in 9 patients, low back pain, paresthesia and spinal root signs in 7 patients. False-negative interpretation of myelography in 2 patients with positive MR findings, and the impressive sensitivity of gadolinium Dota to improve visualization of subarachnoid spread, favor MRI as an alternative imaging technique in the assessment of patients with suspected intradural extramedullary malignancy.
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PMID:Spinal leptomeningeal neoplastic disease. Evaluation by MR, myelography and CT myelography. 131 84

A 42-year-old female case of HTLV-I associated myelopathy (HAM) combined with adult T-cell leukemia (ATL) was reported. The patient noticed paresthesia in the soles at the age of 17, and gait disturbance and urinary retention at the age of 20. These symptoms progressed slowly. The patient showed indurations in both hypothenar regions and leukocytosis of 17,900/microliters in the peripheral blood at the age of 41. On admission to our hospital, she had spastic gait, muscle weakness of four extremities, increased deep tendon reflexes, pathologic reflexes, mild decreased of vibration sense and vesico-rectal disturbance. Anti-HTLV-I antibody (PA method) was increased to 1,024 fold in serum and 64 fold in spinal fluid. Thus, this patient was diagnosed as having HAM. In addition, leukocyte count in the peripheral blood was increased to 17,200/microliters including 33% atypical lymphocytes, and lymphocytes subset analysis showed 96.1% CD4+, 1.8% CD8+ and marked increase in CD4/CD8 ratio. Southern blot analysis of HTLV-I provirus DNA in the lymphocytes was of complete type with a monoclonal mode of integration. These findings indicated a diagnosis of ATL for this patient. HLA typing revealed A2, A11, Bw22, Bw46, Cw1, Cw3, being compatible with HAM type reported by Usuku et al. HAM and ATL were reported to be caused by an identical virus. However, there has been no case report of combination of the two diseases. Usuku et al proposed that the development of each disease was based on the differences in HLA haplotypes and HTLV-I-specific immune responsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[HTLV-I associated myelopathy (HAM) with adult T-cell leukemia (ATL)]. 279 8

The oral signs and symptoms of acute leukemia include gingival hypertrophy, gingival hemorrhage, petechiae and ecchymoses, mucosal ulceration, paresthesia, tooth pain, and oral infections. This case was unusual in that the diagnosis of acute leukemia was made only after a biopsy specimen of tissue protruding from the socket of a recently extracted tooth disclosed malignant cells suggestive of leukemia or lymphoma. The diagnosis of epulis granulomatosa should be made only after clinical, radiographic, and microscopic studies have been performed to rule out a malignant process.
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PMID:Painful, nonhealing, tooth extraction socket. 346 17

Among the neurological side-effects, peripheral neuropathy is a result of therapy with vindesine and above all vincristine. Although in most cases it is responsible only for paresthesias, it may cause extensive paralysis and requires that the drug be discontinued. These drugs may also affect the neurovegetative system. Ototoxicity may be seen with cis-platinum and vigilance disturbances with L-asparaginase. Genetic consequences are mainly due to alkylating agents. These agents almost constantly impair male and female fertility but recovery is possible. Libido is also affected with the attendant psychological consequences. The offspring of patients previously treated by chemotherapeutic agents are normal. Development of secondary carcinoma or leukemia is currently a major concern. Secondary malignant disease may develop after the treatment of any cancer, especially if radiotherapy was associated with alkylating agents. Leukemias are of the acute myeloid type and usually follow a preleukemic phase. A table summarizes the main toxicities of the most usual drugs.
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PMID:[Complications of antitumor and antileukemia chemotherapy. 3 (conclusion)]. 629 11

Twenty-one children (19 with leukemia) were given 34 courses of vindesine on a weekly or twice-weekly schedule in escalating doses. Thirty-three courses were fully or partially evaluable for response and/or toxicity. Granulocytopenia was the dose-limiting toxicity. Transient jaw, neck, or bone pain was common after each dose. Motor weakness, paresthesias, and constipation were neither frequent nor severe. In this Phase I study, vindesine had some antileukemia activity in children previously treated with vincristine and other drugs. Phase II studies are warranted and a starting does of 1.85% mg/m2 twice weekly appears tolerable.
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PMID:Phase I evaluation of vindesine in children: a Southwest Oncology Group pilot study. 719 78

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is an effective drug in the treatment of metastatic breast cancer (MBC). In the salvage setting, 5-fluorouracil (5-FU) and folinic acid have proved to be effective against MBC as well. Recent preclinical data suggest that paclitaxel plus 5-FU has additive cytotoxicity. Given these observations, we initiated a phase II trial in which 38 women with MBC have been treated with a combination of all three drugs. All patients are currently evaluable for toxicity and 34 are evaluable for response. All women had histologically proven and assessable disease. Patients with prior exposure to paclitaxel were ineligible. Patient characteristics include a median age of 51 years (age range, 31 to 73 years) and a median performance status of 1 (range, 0 to 2). Thirty-three patients have received prior chemotherapy, of whom 23 had adjuvant chemotherapy only. Fifty-eight percent of the patients (22 of 38) had received prior doxorubicin or mitoxantrone; four patients had only hormonal therapy. Four patients had bone-only disease, and three patients had lymphangitic spread or cytologically positive pleural effusion as the only evaluable disease. Treatment consisted of paclitaxel 175 mg/m2 over 3 hours (day 1 only), followed by folinic acid 300 mg over 1 hour, followed by 5-FU 350 mg/m2 on days 1 to 3. Patients received standard paclitaxel premedications. To date, 175 cycles have been administered (median cycle length, 29 days; median number of cycles per patient, five). Toxicities included grade 3/4 infections in nine cycles (5%), grade 3/4 mucositis in three cycles, grade 3/4 nausea/vomiting in three cycles, grade 1 paresthesias in 12 patients (32%), alopecia 100%, and 17 cycles (10%) associated with dose reduction. Based on Cancer and Leukemia Group B toxicity criteria, arthralgia/myalgias were modest and graded mild (32 cycles), moderate (nine cycles), or severe (two cycles). There were two major hypersensitivity reactions, prompting removal of those patients from further protocol treatment. Four patients are unassessable for response due to hypersensitivity reactions (two) and unevaluable disease (two). Among the 34 patients evaluable for response, there were three complete responses, 18 partial responses, one minor response, nine stable disease, and three progressive disease (response rate, 62%). Responses were seen in patients who had received prior doxorubicin or mitoxantrone (11 of 22 patients) and in anthracycline/naive patients (10 of 16 patients). Responses were observed in all metastatic sites: soft tissue, viscera, and bone. Paclitaxel/5-FU/folinic acid appears to be an effective and well-tolerated outpatient regimen for women with MBC, even after failure of anthracycline-containing therapy.
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PMID:Paclitaxel and 5-fluorouracil in metastatic breast cancer: the US experience. 862 38

The 'gold standard' for the treatment of polycythemia vera (PV) is to date undefined. We performed a retrospective analysis to evaluate the outcome of a cohort of PV patients treated with pipobroman (PB) at a single institution during a period of 20 years (November 1971-October 1991). During this period, a total of 366 adult PV patients were diagnosed according to Polycythemia Vera Study Group (PVSG) criteria. Of these, only 199 (54%) were treated with PB: 92 were males and 107 females, median age was 63.0 years (range 25.2-87.3 years). Major clinical characteristics at onset were as follows: 34 (17%) patients had splenomegaly >3 cm below costal margin, 70 (35%) had platelets >600,000/mm3, 79 (40%) had white blood cells >12,000 mm3; 97 (49%) had hypertension, 83 (42%) had minor neurological symptoms (as vertigo, headache, paresthesias), 33 (17%) had pruritus and 27 (13%) had thrombotic features. All patients received PB at the dosage of 1 mg/kg/day until response was achieved (hematocrit value <50% in males and <45% in females). Thereafter treatment was given according to toxicity and maintenance of response. All patients were phlebotomized before starting treatment (mean number of phlebotomies performed: three, range 2-4) and 47 of them received PB when hematocrit value was already reduced at response levels: therefore, while all patients are evaluable for acute and long-term toxicity, only 152/199 (76.4%) patients are evaluable for response to PB. During a median time of 2 months, all these 152 patients achieved the response; as maintenance, 128/199 (64.3%) patients were managed with PB alone and 71/199 (35.7%) patients received phlebotomies occasionally. Sixty-one out of 199 (30.6%) patients developed disease-related complications (25 neurological symptoms, 21 thrombotic complications, 12 cardiovascular problems, three hepatic failures). Eleven (5.5%) patients developed acute myelogenous leukemia (AML) after a median time of treatment of 89 months (range 33-188 months), 11 (5.5%) patients developed myelofibrosis (median time from treatment 71 months, range 31-182 months) and in six (3%) patients cancer occurred (median time from treatment 85 months, range 13-118 months). The cumulative risk of leukemia in PV was 2% (95% CI: 0-4%) and 6% (95% CI: 1-11%) at 5 and 10 years respectively; the cumulative risk of myelofibrosis was 2% (95% CI: 1-5%) and 9% (95% CI: 3-15%) at 5 and 10 years, respectively. As of May 1996, 33 (16.6%) patients are lost to follow-up, 40 (20.1%) are dead and 126 (63.3%) are alive with a median overall survival of 191 months. In conclusion, this retrospective analysis confirms the efficacy and safety of PB in PV patients and its low leukemogenic role; prospective studies are needed to evaluate the real impact of PB in the treatment of PV.
Leukemia 1998 Jun
PMID:Polycythemia vera treated with pipobroman as single agent: low incidence of secondary leukemia in a cohort of patients observed during 20 years (1971-1991). 963 13

PSC 833 (Valspodar) can reverse multidrug resistance (MDR) in patients with hematologic malignancies, but alters the pharmacokinetics of concomitant anticancer agents. A phase I, dose-finding study was initiated to define a safe and effective regimen of mitoxantrone, etoposide, and cytarabine (MEC) when administered with PSC 833 to patients with early relapsed or refractory acute myeloid leukemia (AML). Poor-prognosis AML patients refractory to first-line induction therapy or relapsing within 9 months of attaining complete remission (CR) were treated with cytarabine (1.0 g/m2/day), etoposide (30 mg/m2/day), and mitoxantrone at a dose of either 3.0 mg/m2/day (cohort 1) or 4.5 mg/m2/day (cohorts 2 and 3) for 6 days plus continuous-infusion PSC 833 (10 mg/kg/24 h with a 2.0 mg/kg loading dose) for 6 or 7 days each 21-day cycle. Patients achieving CR were given a 4-day MEC plus PSC 833 consolidation cycle. Twenty-three patients were enrolled (eight with primary refractory AML and 15 in relapse). Dose-limiting toxicity occurred in one of six patients in cohort 2 (grade 4 mucositis) and one of seven patients in cohort 3 (grade 4 hyperbilirubinemia). The maximum tolerated dose of mitoxantrone was defined as 4.5 mg/m2/day. Clinically significant grade 4 hyperbilirubinemia, possibly related to PSC 833, occurred in four patients. Hematologic toxicities were as expected in this patient population, but were not dose limiting. Mild to moderate cerebellar ataxia and paresthesia occurred in six (26%) and five (22%) patients, respectively, but were not dose limiting. Overall, six of 23 (26%) patients achieved CR, including five patients with demonstrated P-glycoprotein expression and/or function. The median overall survival was 4 months. All six patients with a CR were alive and four (17%) patients were disease free at 12 months. Blood levels of PSC 833 were well above the target level of 1000 ng/ml, a concentration that is known to reverse MDR in vitro. PSC 833 reduced the clearance of etoposide by approximately two-fold. No correlation was observed between the mitoxantrone or etoposide area under the curve and response. In conclusion, the MEC plus PSC 833 tested regimen was well tolerated and the 26% CR rate warrants further testing of this regimen in a randomized, phase III trial.
Leukemia 2001 May
PMID:Combined action of PSC 833 (Valspodar), a novel MDR reversing agent, with mitoxantrone, etoposide and cytarabine in poor-prognosis acute myeloid leukemia. 1136 37


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