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Biomedical subjects

L Lutz

Publications and source records attributed to L Lutz.

16 recordsLinked to original sources
PubMed2004

Breakthrough pain characteristics and syndromes in patients with cancer pain. An international survey.

Breakthrough pain (BKP) is a transitory flare of pain that occurs on a background of relatively well controlled baseline pain. Previous surveys have found that BKP is highly prevalent among patients with cancer pain and predicts more severe pain, pain-related distress and functional impairment, and relatively poor quality of life. An international group of investigators assembled by a task force of the International Association for the Study of Pain (IASP) evaluated the prevalence and characteristics of BKP as part of a prospective, cross-sectional survey of cancer pain. Fifty-eight clinicians in 24 countries evaluated a total of 1095 patients with cancer pain using patient-rated items from the Brief Pain Inventory (BPI) and observer-rated measures. The observer-rated information included demographic and tumor-related data, the occurrence of BKP, and responses on checklists of pain syndromes and pathophysiologies. The clinicians reported BKP in 64.8% of patients. Physicians from English-speaking countries were significantly more likely to report BKP than other physicians. BKP was associated with higher pain scores and functional interference on the BPI. Multivariate analysis showed an independent association of BKP with the presence of more than one pain, a vertebral pain syndrome, pain due to plexopathy, and English-speaking country. These data confirm the high prevalence of BKP, its association with more severe pain and functional impairment, and its relationship to specific cancer pain syndromes. Further studies are needed to characterize subtypes of BKP. The uneven distribution of BKP reporting across pain specialists from different countries suggests that more standardized methods for diagnosing BKP are needed.

Analysis of Variance↗
PubMed2001

Sneddon's syndrome: a case report.

We report a case of Sneddon's syndrome with the triad of livedo reticularis, hypertension, and neurologic symptoms. The procedures for diagnosis and the tests to delineate clotting abnormalities are examined.

Adult↗
PubMed1997

Efficacy of systemic administration of irinotecan against neuroblastoma xenografts.

The efficacy of the topoisomerase I inhibitor 7-ethyl-10-(4-[1-piperidino]-1-piperidino)-carbonyloxy-camptotheci n (irinotecan, CPT-11) has been examined against a panel of six independently derived neuroblastoma xenografts. Intensive courses of therapy, where irinotecan was administered i.v. daily 5 days per week for two consecutive weeks [(dx5)2; defined as 1 cycle], were compared to more protracted low-dose schedules where cycles were repeated every 21 days for a total of three courses ¿abbreviated [(dx5)2]3¿. When administered (dx5)2 for a single cycle, the maximum tolerated daily dose was 40 mg/kg. Irinotecan induced a high frequency of complete regressions (CRs) in four of the six lines examined; however, most tumors achieving CR regrew during the period of observation (12 weeks). Furthermore, there was no advantage in high-dose regimens as compared to low dose (10 mg/kg) on the same schedule. Protracted schedules of administration, where three courses of therapy were given at 21-day intervals ¿[(dx5)2]3¿ i.v. were examined at 10 and 5 mg/kg/dose. Even at the lower dose level, irinotecan caused 100% CR in all tumor lines that were maintained at 12 weeks. To determine the minimum dose levels required to induce objective regressions of neuroblastoma xenografts, decreasing doses were examined using the [(dx5)2]3 i.v. schedule. At 2.5 mg/kg/dose, >90% of NB-1643, NB-1691, NB-1382.2, and NB-EB xenografts demonstrated CR, whereas at 1.25 mg/kg/dose, all six tumor lines evaluated demonstrated objective regressions (>/=50% volume reduction), with a high frequency of CRs in four tumor lines. The 10-hydroxy-7-ethyl CPT lactone single-day systemic exposure measured with the minimum dose (2.5 mg/kg) associated with complete response was 198, 257, and 228 ng.h/ml for mice bearing NB-1643, NB-1691, and NB-EB tumors, respectively. These results indicate that childhood neuroblastoma xenografts are highly sensitive to irinotecan given by parenteral administration, and that efficacy is schedule dependent.

Animals↗
PubMed1996

Evaluation of irinotecan in combination with 5-fluorouracil or etoposide in xenograft models of colon adenocarcinoma and rhabdomyosarcoma.

Irinotecan [7-ethyl-10-(4-[1-piperidino]-1-piperidino)-carbonyloxy-camptothec in] administered i.v. in two courses, each course consisting of administration every day for 5 days [(dx5)2] on days 1-5 and 8-12, has demonstrated significant activity against advanced human tumor xenografts derived from colon adenocarcinomas and several childhood cancers. To build on this therapy, we have evaluated the combination of irinotecan given on this schedule with 5-fluorouracil given on days 1, 7, and 14 with or without leucovorin [(dx5)3 i.v.] against colon tumors, or combined with etoposide administered (dx5)2 i.v. either 2 h before or 2 h after irinotecan for treatment of colon tumors and rhabdomyosarcomas. A combination of 5-fluorouracil at 75% and irinotecan at 50% of their respective maximum tolerated doses when administered as single agents on this schedule gave acceptable toxicity. Against colon adenocarcinoma xenografts, 5-fluorouracil did not enhance the response rate compared with that obtained with the optimum dose of irinotecan given as a single agent. Against GC3/TK- xenografts, which lack thymidine kinase and cannot salvage thymidine to circumvent the inhibition of thymidylate synthase, the addition of leucovorin to the combination increased the complete response rate from 10 to >90%, whereas the response rates for the optimal doses of irinotecan or 5-fluorouracil, as single agents, were 30 and <10%, respectively. Etoposide d x 5 i.v. for two or three courses or (d x 5)3 p.o. did not cause objective regression of any colon tumors. In contrast, three of five rhabdomyosarcoma lines demonstrated a high frequency of partial regressions or complete regressions when treated (d x 5)1 i.v. Repetitive courses [e.g., (d x 5)2 or (d x 5)3] i.v. or p.o. or by 4-h infusion d x3 i.v. were either equally effective or less effective. Irinotecan and etoposide were combined using the (d x 5)2 i.v. schedule for both drugs, in which irinotecan was given 2 h before or 2 h after the administration of etoposide. Each drug could be combined at only 38% of its respective maximum tolerated dose when administered as a single agent, indicating greater than additive toxicity. Toxicity was similar irrespective of the sequence of administration and was manifested by loss of weight (73% of the initial weight, nadir day 7), myelosuppression, and prolonged thrombocytopenia. The responses of colon carcinomas to the combination given in either sequence were similar to that achieved with irinotecan given alone at the same dose as used in the combination. Similarly, when etoposide was given before irinotecan, the responses of rhabdomyosarcomas were similar to those for irinotecan. However, in experiments in which etoposide was administered 2 h after each dose of irinotecan, there was significant antagonism of the antitumor activity of irinotecan.

Adenocarcinoma↗
PubMed1995

Efficacy of topoisomerase I inhibitors, topotecan and irinotecan, administered at low dose levels in protracted schedules to mice bearing xenografts of human tumors.

The efficacy of protracted schedules of therapy of the topoisomerase I inhibitors 9-dimethyl-aminomethyl-10-hydroxycamptothecin (topotecan) and 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin (irinotecan; CPT-11) were evaluated against a panel of 21 human tumor xenografts derived from adult and pediatric malignancies. Tumors included eight colon adenocarcinomas, representing an intrinsically chemorefractory malignancy, six lines derived from childhood rhabdomyosarcoma (three embryonal, three alveolar) representing a chemoresponsive histiotype, sublines of rhabdomyosarcomas selected in vivo for resistance to vincristine and melphalan, and three pediatric brain tumors. All tumors were grown at the subcutaneous site. Topotecan was administered by oral gavage 5 days per week for 12 consecutive weeks. The maximum tolerated dose (MTD) was 1.5 mg/kg per dose. Irinotecan was given by i.v. administration daily for 5 days each week for 2 weeks [(d x 5)2](one cycle of therapy), repeated every 21 days. The MTD for three cycles was 10 mg/kg per dose. Treatment was started against advanced tumors. Topotecan caused a high frequency of objective regressions in one of eight colon tumor lines, whereas irinotecan caused complete regressions (CR) of all tumors in three colon lines and a high frequency of CRs in three additional lines. Both drugs demonstrated similar activity against rhabdomyosarcoma xenografts. Topotecan caused CR of all tumors in four of six lines, and irinotecan in five of six lines evaluated. Both agents retained full activity against tumors selected for primary resistance to vincristine, but only irinotecan retained activity against a tumor selected for primary resistance to melphalan. Both agents demonstrated good activity against brain tumor xenografts with irinotecan causing CR in two of three lines and topotecan inducing CR in one of three lines. Results indicate that low-dose protracted schedules of daily administration of these topoisomerase I inhibitors is either equi-effective or more efficacious than more intense shorter schedules of administration reported previously.

Adenocarcinoma↗
PubMed1995

Efficacy of sulofenur and a second generation diarylsulfonylurea, N-[5-(2,3-dihydrobenzofuryl)sulfonyl]-N'-(3,4-dichlorophenyl)urea (LY295501), against colon adenocarcinoma xenografts.

Sulofenur and a second generation diarylsulfonylurea (DSU), N-[5-(2,3-dihydrobenzofuryl)sulfonyl]-N'-(3,4-dichlorophenyl)urea (LY295501), were evaluated against a panel of eight colon adenocarcinoma xenografts. Of these tumors, four were derived from adult patients and four from young patients (age range 11-26 years). Both drugs were administered twice daily by oral gavage, 5 days each week for two or three consecutive weeks. The maximum tolerated dose for sulofenur was 300 mg/kg/dose for three courses and 200 mg/kg/dose for LY295501. Against 'adult' derived tumors, sulofenur caused a high proportion of objective regressions of advanced xenografts in two of four lines, with significant inhibition of growth in three tumor lines. Colon adenocarcinomas from young patients were similarly sensitive to sulofenur with a high proportion of complete and partial responses in two of three lines. LY295501 demonstrated a very similar spectrum of activity against this panel of xenografts. Tumors intrinsically resistant to sulofenur were resistant to LY295501, although this agent was slightly more active than sulofenur against tumors from younger patients. In addition, xenografts were established from a cloned colon adenocarcinoma line (GC3/c1) and its derivative GC3/LYC5) selected in vitro for resistance to sulofenur. GC3/c1 xenografts were highly responsive to both sulofenur and LY295501, whereas GC3/LYC5 xenografts were completely resistant to both agents administered at the maximum tolerated dose and schedule. These results indicate that the second generation DSU, LY295501, demonstrates a similar spectrum of activity against colon tumors as does sulofenur, and that the mechanism of action and/or resistance to the two drugs is probably similar.

Adenocarcinoma↗