Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Childrens Cancer Study Group (CCSG) undertook a study (CCG-823F) to test the feasibility of administering continuous infusion doxorubicin (CI DOX) and cisplatin (CDDP) in patients with unresectable or incompletely resected hepatoblastoma (HB) or hepatocellular carcinoma (HCC). Chemotherapy consisted of CI DOX 20 mg/m2/d for days 1 to 4 and CDDP 100 mg/m2 on day 1 followed by a 21-day rest period. Second-look surgery was performed after the administration of four chemotherapy courses. Forty-seven (47) assessable patients were entered on study, 33 with HB and 14 with HCC; of these, 34 (26 HB and eight HCC) completed the initial four courses of chemotherapy. Of the 26 HB patients, 25 were evaluated as responding to chemotherapy before the scheduled second-look procedure and were considered surgically resectable at that time. Surgery was performed on 22 patients; three patients refused the second-look surgery. Nine patients had no evidence of residual malignant disease, seven underwent surgical resection of remaining tumor, four were left with microscopic residual disease, one had a partial resection with gross tumor left behind, and one remained unresectable. Nine HCC patients completed four chemotherapy courses. Eight patients achieved a partial remission and second-look surgery was attempted on seven. Only two had all malignant disease removed at the second procedure. Data from 225 courses of chemotherapy were evaluated for toxicity. Neutropenia (absolute granulocyte count less than 500/mL) was observed in 68 courses, and five of these episodes were associated with sepsis. Severe mucositis was documented in 21 courses, and hypomagnesemia (magnesium less than 1.2 mg) was noted in 30 patients. Two patients developed decreased left ventricular shortening fraction, which resolved when chemotherapy was discontinued. In summary, CI DOX plus CDDP is a well-tolerated and effective regimen in inducing surgical resectability in HB patients who are unresectable at diagnosis and significantly improves survival for this group of patients to 66.6%.
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PMID:Effective treatment of unresectable or metastatic hepatoblastoma with cisplatin and continuous infusion doxorubicin chemotherapy: a report from the Childrens Cancer Study Group. 172 Apr 52

Neuraxis radiation therapy (RT) for primary intracranial tumors is associated with major late effects if administered to very young children. To control residual tumor and to delay RT, we treated eight young children (median age 6.5 months) with primary central nervous system (CNS) tumors using combination chemotherapy: cisplatin, 20 mg/M2/day plus VP-16, 75 mg/M2/day i.v. for 5 days, given q. 3-6 weeks for 8 cycles. The tumors were medulloblastoma (one), malignant ependymoma (two), primitive neuroectodermal tumor PNET (two), malignant glioma (two), astrocytoma (one). Six had measurable disease; three had positive cerebrospinal fluid (CSF) cytopathology. All patients with measurable tumor had initial objective responses (three) complete response [CR], one partial response [PR], two minor response [MR], including cytopathology (three CR of three) and metastatic deposits (two CR of two). One patient relapsed during chemotherapy. Median time to disease progression was 17.5 months; median survival was 34 months. Three patients, none of whom received RT, have prolonged progression-free intervals of 47-67 months to date. Neurodevelopmental progress continued during and after chemotherapy. Chemotherapy toxicity was mild. Median neutrophil nadir was 312/mm3, platelets 72,000. Fever during neutropenia occurred in six of 61 courses. Moderate high-frequency auditory losses were detected in three patients, and mild renal injury (GFR less than 70 ml/min) was detected in two of seven evaluable children. This pilot study demonstrates the apparent efficacy and mild toxicity of 5 day courses of cisplatin plus VP-16, with delayed RT, in young children with CNS neoplasms. A POG treatment protocol that incorporates cisplatin plus VP-16 is evaluating primary chemotherapy with delayed radiotherapy in larger numbers of pediatric brain tumor patients.
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PMID:Efficacy of postoperative chemotherapy using cisplatin plus etoposide in young children with brain tumors. 199 Feb 53

Medulloblastoma, pineoblastoma, and cerebral neuroblastoma are malignant embryonal tumors of the CNS that may demonstrate similar histologic features, a propensity for neuraxis dissemination and sensitivity to radiation therapy and, in certain cases, chemotherapy. To evaluate the activity of preirradiation chemotherapy in such tumors, 11 newly diagnosed children with measurable residual disease and characteristics indicative of poor prognosis were treated postoperatively with cisplatin (CDDP) and etoposide (VP-16). Responses graded on the basis of radiographic findings in areas of either macroscopic residual tumor or metastatic disease included two complete responses (CRs), eight partial responses (PRs), and one stable disease (SD). Acute and subacute toxicity consisted of high-frequency hearing loss in four patients, reversible signs and symptoms of increased intracranial pressure in two patients, and transient neutropenia. Seven of eight patients with high-risk medulloblastoma and two of two with pineoblastoma remain free of tumor progression following neuraxis irradiation at 8 to 48 months postdiagnosis (median, 18 months). CDDP and VP-16 is a highly active drug combination when given before irradiation in children with high-risk medulloblastoma and other malignant embryonal tumors of the CNS, producing objective responses in at least one site of measurable disease in 10 of 11 newly diagnosed patients, including all of five with gross neuraxis dissemination.
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PMID:Preirradiation cisplatin and etoposide in the treatment of high-risk medulloblastoma and other malignant embryonal tumors of the central nervous system: a phase II study. 215 66

Twenty-three patients with marginally resectable and unresectable non-small-cell lung cancer (stages IIIA and IIIB) were treated by neoadjuvant chemotherapy. All patients received three cycles of preoperative chemotherapy with two alkylating agents, cyclophosphamide 2.5 g/m2 intravenously (i.v.) and ifosfamide 3.5 g/m2 i.v., mesna 12 g/m2 was given additionally to prevent drug hematuria. Six of 23 patients (26%) had partial response. Of the seven patients who underwent thoracotomy, two were completely resected, but with macroscopic residual disease. Mean time to progression for the whole group was 7 months. Fifteen patients had progression of disease, with local metastases only in six, and distant metastases in eight. After administering 52 chemotherapy cycles, cyclophosphamide-ifosfamide doses were cut down, as eight of 16 patients required hospitalization for fever during neutropenia nadirs. This two-alkylating (non-cisplatin) regimen, unlike cisplatin-based regimens, was ineffective, and further trials are not recommended.
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PMID:Cyclophosphamide and ifosfamide combination as neoadjuvant chemotherapy for locally advanced nonsmall-cell lung cancer: a meta-analytic review. 217 Jul 71

The efficacy and toxicity of the new anthracycline, 4'-0-tetrahydropyranyl doxorubicin (THP) (50 mg/m2 intravenous [IV] bolus) in association with cisplatin (100 mg/m2 IV as a 4-hour infusion) was assessed in 31 patients with advanced ovarian carcinoma. Twenty-eight patients were assessable for toxicity among whom 25 were assessable for response (International Federation of Gynecology and Obstetrics [FIGO] stage IIIa, four patients; IIIb, 15 patients; IV, six patients). Nine patients had received prior treatment. Patients were randomized to receive schedule (sch) A (THP at 6 hours, then cisplatin from 16 to 20 hours) or sch B (THP at 18 hours, then cisplatin from 4 to 8 hours). Sch A was hypothesized as less toxic since THP was best tolerated in the late rest span and cisplatin near the middle of the activity span in experimental studies. The rate of clinical complete response (CR) was 52%, that of partial response (PR) was 12%, and the overall clinical response rate (CR plus PR) was 64% (sch A, 73%; sch B, 57%). Median progression-free survival and survival times were, respectively, 10 and 19 months. Of 12 patients in clinical CR evaluated at second-look laparotomy, four had a pathological CR (33%), and three had microscopic residual disease (MD). The overall rate of pathological CR was 16%. Sch A was associated with less neutropenia (P = .10), thrombocytopenia (P less than .01), anemia (P less than .01), and renal toxicity (P less than .05) than sch B. Of four patients withdrawn for toxicity, three were on sch B (one death). Mean dose intensities (DIs) of THP and cisplatin, respectively, decreased by 30% and 47% over the five initial courses. Such decrease was significantly more pronounced for sch B than for sch A in previously untreated patients (P from 2-way analysis of variance [ANOVA] less than .01). THP-cisplatin is active against advanced ovarian cancer, and its toxicities can be significantly decreased by dosing THP in the early morning and cisplatin in the late afternoon as compared with THP in the evening and cisplatin the next morning.
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PMID:Chemotherapy of advanced ovarian cancer with 4'-O-tetrahydropyranyl doxorubicin and cisplatin: a randomized phase II trial with an evaluation of circadian timing and dose-intensity. 217 81

We treated 25 newly diagnosed patients with advanced epithelial ovarian cancer with an intensive induction chemotherapy regimen using high-dose cisplatin in combination with cyclophosphamide and doxorubicin. All patients had either stage IIIC or stage IV disease. Two intensive induction courses of chemotherapy were administered at 28-day intervals, which consisted of cisplatin 40 mg/m2 daily for 5 days, cyclophosphamide 500 mg/m2 day 1, and doxorubicin 40 mg/m2 day 1. Four courses of chemotherapy using cisplatin 60 mg/m2, doxorubicin 40 mg/m2, and cyclophosphamide 500 mg/m2 followed the high-dose induction therapy. Two of the first six patients died during high-dose induction therapy (one died of neutropenia and sepsis, one of intercurrent intracerebral hemorrhage). Doxorubicin was subsequently omitted from the induction therapy due to unacceptable myelosuppression; no deaths occurred in the remaining 19 patients, and myelosuppression was manageable. Peripheral neuropathy was the most severe side effect with this regimen. This complication was unpredictable, developed during the third or fourth month of treatment, and was disabling in five patients. Other toxicity included prolonged nausea and vomiting (eight patients), ototoxicity (five patients), and nephrotoxicity (two patients), but these did not compromise therapy. All 23 assessable patients had objective response to therapy. Four of 12 patients who underwent second-look laparotomy had pathologic complete response, while four additional patients had only microscopic residual disease. The median survival for the entire group was 25 months. Four patients remain continuously disease-free 23 to 48 months following completion of therapy. Although this regimen was tolerated by most patients, the unpredictable occurrence of disabling neuropathy may limit its usefulness.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High-dose cisplatin combination chemotherapy in the treatment of advanced epithelial ovarian carcinoma. 211 72

Fludarabine was used to treat 68 patients with previously treated chronic lymphocytic leukemia (CLL). Nine (13%) patients achieved a complete remission and 30 (44%) a partial remission. The response rates for Rai stages 0 to 2, 3, and 4 were 64%, 58%, and 50% respectively. Seventeen (43%) of the 40 Rai stage 1 to 3 patients and four (19%) of the Rai stage 4 patients returned to Rai stage 0. Survival was strongly correlated with the final Rai stage achieved. The survival of the 11 partial responders with residual disease consisting only of residual bone-marrow nodules was similar to the complete responders (36+ months) and superior to the other partial response patients (16 months). The response to fludarabine was rapid, with 36 (92%) of the 39 responders having achieved at least a partial response following the first three courses. Complete responses occurred in the blood, liver, spleen, and lymph nodes in 48% to 69% of the patients. Eradication of all disease in the bone marrow occurred in only 13% of the cases. Neutropenia and thrombocytopenia occurred in 56% and 25% of evaluable courses. Major infections occurred in 9% of evaluable courses and fevers of unknown origin or minor infections in 12% of courses respectively. Myelosuppression and infection were more common in patients with initial Rai stages 3 and 4 and in nonresponding patients. Other toxicity was mild. No CNS toxicity was noted.
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PMID:Fludarabine: a new agent with major activity against chronic lymphocytic leukemia. 247 95

One hundred and six patients with stage Ic to IV ovarian carcinoma were treated by a protocol consisting of optimal debulking surgery followed by 9 cycles of CHAP chemotherapy. Clinical response was confirmed by a second-look procedure. Sixty-nine patients (65%) responded with 54 histological complete remissions (50.8%). Nineteen patients did not receive any complementary treatment due to a negative reaction, or prolonged neutropenia. Seven patients received maintenance chemotherapy, 10 an abdominal radiotherapy, 22 intraperitoneal chemotherapy and 11 autologous bone marrow transplantation. The 5-year survival rate was 32.5% and disease-free survival rate was 39.7%. Prognostic-factor analysis showed that age, initial staging, residual disease and cytological grading were significant. The authors propose a classification based on the risk of relapse, and different therapeutic indications for improving response rate and patient survival.
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PMID:[Results of cisplatin-based polychemotherapy and analysis of prognostic factors in ovarian cancer. Apropos of 106 cases]. 263 36

We conducted a prospective, randomized study to clarify the role of radiotherapy of the primary tumor in limited small-cell cancer of the lung. After stratification for sex and for performance score based on the ability to ambulate, patients were randomly assigned to receive initial radiotherapy plus chemotherapy, delayed radiotherapy plus chemotherapy, or chemotherapy alone. The chemotherapy consisted of cyclophosphamide, etoposide (VP-16-213), and vincristine, with doxorubicin subsequently replacing etoposide in alternate cycles 7 through 18. Chemotherapy was given every three weeks for 18 months. The radiotherapy comprised 4000 rad in four weeks, followed by a 1000-rad "boost" directed against residual disease. All patients received prophylactic whole-brain radiation. The patients enrolled totaled 426, and 399 were evaluable. There was a statistically significant difference in the frequency of complete responses in favor of the two radiotherapy regimens (P = 0.0013). Failure-free survival was also longer with these two regimens (P less than 0.001), as was the interval before treatment failure in the chest (P less than 0.001) and overall survival (P = 0.0099). As expected, toxic effects--chiefly neutropenia--were also increased. The addition of radiotherapy of the primary tumor to combination chemotherapy improved both complete-response rates and survival, with increased but acceptable toxicity.
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PMID:Chemotherapy with or without radiation therapy in limited small-cell carcinoma of the lung. 302 92

The development of a new multidrug chemotherapy regimen for primary brain tumors was based upon the cellular heterogeneity within individual tumors, the Goldie-Coldman and Price-Goldie-Hill hypotheses, and known agonistic effects of certain drug combinations and sequences. Eight drugs (vincristine [VCR], hydroxyurea, procarbazine, CCNU, cisplatin, cytosine arabinoside [Ara-C] high-dose methylprednisolone, and either cyclophosphamide or dacarbazine) were administered within 12 hours in an attempt to minimize myelosuppression. Courses were repeated at 2- to 4-week intervals. The regimen was devised to include lipid and water soluble drugs, polar and nonpolar agents, phase-specific and cell-cycle independent agents, and antineoplastics with different mechanisms of action. More than 330 courses of the regimen were administered to 107 children with brain tumors whose tumor had recurred or had been incompletely resected at diagnosis. Tumor response according to protocol-specified criteria and independent review was evaluable in 78% of the patients. After just two cycles of chemotherapy and within a 4- to 6-week interval, 50% had an objective tumor response including 15.5% who had a complete response (CR). Nephrotoxicity and high-frequency hearing losses were noted after three to five courses of therapy in approximately half of the patients. Transfusions with red cells or platelets and use of antibiotics for fever and neutropenia were required in 10% to 25% of patients. The regimen appears satisfactory for preradiation chemotherapy in newly diagnosed patients with residual tumor after surgery, but it must be compared with standard therapeutic approaches in prospective controlled trials before its relative value can be established.
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PMID:Eight drugs in one day chemotherapy for brain tumors: experience in 107 children and rationale for preradiation chemotherapy. 304 Sep 19


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