Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Six Caribbean patients with histologically and immunologically characterized adult T-cell leukemia/lymphoma (ATL) were treated intravenously (IV) with 2'-deoxycoformycin (DCF) at a dose of 5 mg/m2 on days 1, 2, 8, 15, and 22 with four additional weekly doses to convert any partial responses (PR) to complete responses (CR). Patients were considered eligible for this study if refractory to or relapsed from combination chemotherapy, had a life expectancy of 4 weeks or more, a performance status greater than or equal to 50%, normal renal and hepatic function, and no chemotherapy within 4 weeks. Clinical characteristics of the patients in this study included lymphadenopathy in five patients, skin involvement in four patients, bone marrow infiltration in five patients, and central nervous system involvement in two patients. Circulating ATL cells were present in four patients, and three were hypercalcemic. Of five patients evaluable for response, there was one PR of 1 month, and two minor responses lasting 2 and 3 weeks. The median duration of survival for all treated patients was 3 weeks or more. The DCF was associated with moderate side effects, including conjunctivitis in three patients, nausea and vomiting in two patients, progressive hepatic insufficiency in one patient, and moderate myelotoxicity in three patients. Infections occurred in four patients, including two cases of oral candidiasis and two cases of fatal neutropenic sepsis in patients receiving concurrent intrathecal methotrexate. As a single agent, DCF appears to have limited activity in advanced refractory/relapsed ATL. Studies in the future should explore DCF in combination with other cytotoxic agents as initial therapy in better-risk patients.
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PMID:2'-Deoxycoformycin therapy in adult T-cell leukemia/lymphoma. 289 Apr 28

Twenty patients with stage III and IV diffuse well-differentiated lymphocytic lymphoma were treated with combination chemotherapy consisting of BCNU, cyclophosphamide, vincristine, melphalan and prednisone (M-2). Treatment was given every 5 weeks for 11 cycles in responding patients. The median age of the patients was 62 years (range 45-76). There were 12 complete remissions and 6 partial remissions for an overall response rate of 90%. The median duration of remission was 24 months (range 12-79 months) and was identical for complete responders and partial responders. All but 2 responding patients have been subsequently retreated for relapse. The median survival was 84 months (range 1-108 months). Myelosuppression was mild. Nausea/vomiting, neuropathy, alopecia and gastrointestinal symptoms from prednisone were seen in the minority of patients. One patient expired from sepsis/neutropenia during the first cycle of therapy. The M-2 protocol produces effective remissions in diffuse well-differentiated lymphocytic lymphoma. The relapse and survival pattern are similar to the results achieved with other chemotherapy regimens in low-grade lymphoma.
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PMID:Diffuse well-differentiated lymphocytic lymphoma: chemotherapy with BCNU, cyclophosphamide, vincristine, melphalan and prednisone. 305 72

The regimen of doxorubicin (DOX), ifosfamide (IFF), and dacarbazine (DTIC) (AID) for previously untreated inoperable or metastatic sarcoma has acceptable toxicity with significant activity. Twenty patients received 79 courses of DOX (60-75 mg/m2) with or without DTIC (900 mg/m2) by continuous infusion over 72 hours with escalating doses of IFF and mesna uroprotection. Nineteen patients were evaluable for toxicity. Myelosuppression was dose-limiting. The maximum tolerated dose was DOX at 60 mg/m2, DTIC at 900 mg/m2, and IFF at 7500 mg/m2 per course. Of the 79 courses analyzed, 33 (42%) resulted in wbc counts less than 1000/microliter; 14 (18%) were complicated by fever and neutropenia, and three by sepsis. There were no toxic deaths. Relative platelet sparing was observed and nadirs were brief. In contrast to bolus-dose DTIC divided over 5 days, DTIC by continuous infusion did not add significantly to gastrointestinal toxicity. Nausea and vomiting was well controlled by antiemetics. Mucositis occurred sporadically. Unlike our phase II study of IFF alone, no CNS or renal toxicity was observed. No cardiac toxicity was encountered, although only four patients have received greater than 450 mg/m2 of cumulative DOX. One episode of DOX extravasation occurred despite a long iv line that extended to the axilla. No serious tissue damage was observed, perhaps due to the dilute solutions of DOX used. Partial responses were seen in eight of 18 evaluable patients (44%) and in six of 11 patients at or near the phase II level. Two additional patients with minimal response have continued tumor regression. The median number of courses before partial response was four (range, one to five). The median duration of response has not been reached (3+ to 10+ months). An inoperable primary has been rendered surgically resectable in one patient. Activity in previously untreated sarcomas should be further evaluated in a randomized phase III study against a standard DOX-containing combination.
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PMID:Doxorubicin, ifosfamide, and dacarbazine (AID) with mesna uroprotection for advanced untreated sarcoma: a phase I study. 308 17

One hundred twenty-four children and young adults with recurrent tumors, predominantly sarcomas, were treated with the combination of ifosfamide, etoposide, and the uroprotector, mesna (2-mercaptoethane sulphonate), in a phase II trial. The treatment regimen consisted of 12 cycles of therapy administered every 3 weeks. After evaluation of the tumor response to chemotherapy alone, radiation or surgery was used to eradicate residual sites of metastatic disease where possible. At the present time, 77 patients are evaluable for response to the chemotherapy; 43 of the patients have experienced a significant reduction in the tumor size in response to the chemotherapy alone (39 partial responses [PR] and four complete responses [CR]). Sixteen of 17 patients with Ewing's sarcoma, nine of 13 with rhabdomyosarcoma, four of eight with peripheral neuroepithelioma, three of eight with osteosarcoma, and 11 of 31 with other tumors have responded with a PR or CR. The toxicity of the regimen was acceptable. Moderate or severe toxicity evaluated on a per cycle basis included: neutropenia, 97%; thrombocytopenia, 32%; nephrotoxicity, less than 1%; mucositis, 1%; neurologic toxicity, 2%; nausea and vomiting, 13%; hemorrhagic cystitis, less than 1%. Fever was present after 33% of cycles and sepsis following 7%. One patient died due to sepsis and pancytopenia. At the present time, only seven of the 43 patients who responded to the chemotherapy regimen have relapsed, with a median follow-up of 10 weeks after the response. This drug combination is highly active in the treatment of recurrent sarcomas and other tumors in children and young adults.
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PMID:Ifosfamide with mesna uroprotection and etoposide: an effective regimen in the treatment of recurrent sarcomas and other tumors of children and young adults. 311 35

In order to find an effective and suitable chemotherapy regimen for preoperative treatment of esophageal cancer, patients with inoperable or metastatic disease were treated with a combination of etoposide and cisplatin. Of 27 evaluable patients, 13 had squamous cell carcinoma, 13 adenocarcinoma, and 1 muco-epidermoid carcinoma. No complete responses were noted. Nine of 13 patients with squamous cell carcinoma and only one of 13 with adenocarcinoma showed a partial response. Nine of 10 responders achieved a partial response after 2 courses, one after 4 courses. There was one toxic death, due to sepsis during leukopenia. Other toxicities were alopecia, nausea and vomiting, nephrotoxicity, thrombocytopenia and leukopenia.
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PMID:Etoposide and cisplatin in advanced esophageal cancer. A preliminary report. 323 66

CYVADIC (cyclophosphamide + vincristine + adriamycin + dacarbazine = DTIC) is frequently used in the treatment of patients with soft tissue sarcomas or malignant mesotheliomas. As a modification of the protocol originally published by Gottlieb, the interval between two cycles was extended to 4 weeks for better bone marrow regeneration and vincristine was given only once instead of twice per cycle. A total of 237 cycles of this modified CYVADIC protocol resulted in tolerable toxicity (except nausea and vomiting) and therapeutic results comparable to the original protocol (6/22 complete remissions and 6/22 partial remissions in sarcomas; 1/5 partial remission in mesotheliomas). Hematotoxicity was cumulative after 6 CYVADIC cycles. In contrast to the original Gottlieb scheme there were no severe infections such as pneumonia or sepsis. Neurotoxicity was weak and reversible; cardiotoxicity was not observed. Compared to the protocol originally suggested by Gottlieb, the modified CYVADIC regimen appears to be as effective but less toxic.
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PMID:[Toxicity of the CYVADIC modification in patients with soft tissue sarcomas or malignant mesotheliomas]. 331 70

The toxicity of a new chemotherapeutic regimen for CNS tumors using eight anticancer agents administered in a 12-hour period was evaluated in 34 children with newly diagnosed and recurrent tumors treated at the Children's Hospital and Medical Center in Seattle. The chemotherapy included methylprednisolone, vincristine, lomustine (CCNU), procarbazine, hydroxyurea, cisplatin (CDDP), and either cyclophosphamide or imidazole carboximide (DTIC). The first five patients additionally received high-dose methotrexate (HDMTX), but because of excessive toxicity this was replaced by cytarabine. Of 125 courses administered without HDMTX, red cell transfusions were required in 15% of the courses and platelet transfusions were required in 8%. Hospitalization for empiric treatment of fever associated with neutropenia occurred in 6% of courses. Three episodes of documented sepsis occurred. Virtually all hematologic toxicity occurred in patients with recurrent disease. Renal toxicity occurred in 14% of patient courses. One patient died of renal failure and sepsis following therapy. Neurologic and hepatic complications were infrequent. High-frequency hearing loss above the voice range was common, but clinically significant hearing loss occurred in only three patients. Severe nausea and vomiting were infrequent. Overall, the toxicity of "eight in one" chemotherapy in newly diagnosed patients was minimal; toxicity was greater in patients with recurrent disease.
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PMID:Eight drugs in one day chemotherapy in children with brain tumors: a critical toxicity appraisal. 337 69

A combination of mitoxantrone, vincristine, and prednisone was used to treat 19 patients with acute lymphocytic leukemia. Of these, 12 were patients with acute lymphoblastic leukemia (ALL) (9 in first relapse and 5 primarily refractory to standard induction therapy with daunorubicin, vincristine, and prednisone), 2 had a phenotypic ALL relapse after an initial diagnosis of acute myelocytic leukemia and 5 had terminal deoxynucleotidyl transferase positive blastic phase chronic myelogenous leukemia (BCML). Eight patients with ALL (and of these, four with primarily anthracycline resistant disease), and two with BCML achieved complete remission. Five patients died in induction (three ALL from sepsis and two BCML from bleeding), and five had progressive disease. Median duration of response was 5 months, with two primarily refractory ALL patients remaining in continuing complete remission at 28 and 31 months. Treatment was well tolerated, with minimal nausea and vomiting, and oral mucositis. Posttreatment transient hepatic dysfunction was seen in 80% of patients. Mitoxantrone, vincristine, and prednisone are an active combination for the treatment of relapsed or refractory ALL and of terminal deoxynucleotidyl transferase positive BCML. The finding that four of five primarily refractory ALL patients were induced in complete remission supports the contention that mitoxantrone and anthracyclines are not cross-resistant.
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PMID:Mitoxantrone, vincristine, and prednisone in adults with relapsed or primarily refractory acute lymphocytic leukemia and terminal deoxynucleotidyl transferase positive blastic phase chronic myelocytic leukemia. 347 1

In a randomized trial the antineoplastic and toxic effects of doxorubicin (ADR), mitomycin (MMC), and the combination of the two were evaluated in postmenopausal patients with advanced breast cancer using the following treatment regimens: ADR (75 mg/m2 by iv bolus every 3 weeks); MMC (20 mg/m2 by iv bolus every 6 weeks); and ADR (45 mg/m2 by iv bolus every 3 weeks) and MMC (10 mg/m2 by iv bolus every 6 weeks). One hundred one patients were entered in the study. Entrance to single-agent MMC therapy was stopped after allocation of 12 patients because of unacceptable side effects, especially nausea and vomiting, and the suggestion of minor efficacy. One of these patients had partial response, eight had no change, and three had progressive disease. The patients in the ADR and ADR plus MMC group were similar as to the following: age (median, 60 years); menopausal age; disease-free interval; performance status, extent of previous cytotoxic therapy (approximately 90% were pretreated) and radiation therapy; and dominant site of disease but with significantly more involved organ sites in the ADR plus MMC group. Among evaluable patients (42 in the ADR group and 39 in the ADR plus MMC group), response rates were as follows: complete response--21 versus five; partial response--26 versus 44; no change--40 versus 38; and progressive disease--12 versus 13 (P greater than 0.10). Median times to disease progression were 5.2 and 7.8 months, respectively (log-rank test, P = 0.03), but survival times were similar, 9.3 and 10.2 months, respectively (log-rank test, P greater than 0.40). For the two treatment groups suppression of wbc count was similar, while anemia, thrombopenia, and nausea and vomiting were significantly more common among the ADR plus MMC-treated group. Five treatment-induced deaths were observed in the ADR plus MMC group (one from sepsis; two from diffuse hemorrhage; and two from cardiomyopathy), compared to none in the ADR group. In conclusion, this study disclosed no major advantage of the combination of ADR plus MMC compared to ADR alone as second-line treatment of advanced breast cancer, but results from other studies may imply a possible role of MMC as part of second-line combination chemotherapy regimens.
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PMID:Doxorubicin versus mitomycin versus doxorubicin plus mitomycin in advanced breast cancer: a randomized study. 353 Apr 44

Thirty-five patients with previously untreated, advanced, measurable metastatic colorectal carcinoma were treated with a 12-week course of continuous 5-fluorouracil (5-FU) and weekly cisplatin. Twenty of 32 evaluable patients responded (five complete and 15 partial responses), for an overall response rate of 63% (90% confidence limits, 43%-75%). Toxicity was generally mild and reversible and included mucositis (40%), painful erythema of the palmar and plantar skin (30%), diarrhea (21%), nausea and vomiting (15%), and leukopenia (6%). One patient died of sepsis secondary to mucositis and myelosuppression. This program is a well-tolerated outpatient regimen for metastatic colorectal carcinoma. The response rate is higher than expected for 5-FU and cisplatin and suggests clinical therapeutic synergism at this dose rate and schedule.
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PMID:Pilot trial of prolonged continuous-infusion 5-fluorouracil and weekly cisplatin in advanced colorectal cancer. 355 89


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