Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since 1972, the National Surgical Adjuvant Breast and Bowel Project (NSABP) has carried out a series of clinical trials evaluating the worth of adjuvant chemotherapy in the management of patients with primary breast cancer. This report provides information concerning (a) protocol compliance relative to drug administration and (b) acute toxicity encountered by patients in three separate trials who were given one-, two- or three-drug chemotherapy within 1 month of operation. The findings are derived from 1548 women who received 20,765 courses of chemotherapy, the most extensively documented experience yet reported. They indicate that despite the large number of physicians and the heterogeneity of the institutions participating, large cooperative efforts can be accomplished with credibility. Only 13 (0.8%) of the women failed to complete all courses of therapy for reasons directly related to nonprotocol compliance by physicians. Only 4.3% failed to complete therapy for miscellaneous reasons other than toxicity, treatment failure, occurrence of a second primary, or death unrelated to tumor. While almost all patients experienced toxic reactions during the therapy, only 3%--4% of recipients of melphalan (L-PAM; P) and 4%--5% of recipients of L-PAM + 5-FU(F)(PF) failed to complete 2 years of therapy because of toxicity. Of those patients receiving PF + methotrexate (MTX; M) (PMF), 15% did not finish their treatment for that reason. While there was little difference in hematologic and nonhematologic toxicity between those patients receiving P or PF, and such toxicity was generally acceptable to both patients and physicians, the addition of MTX (PMF) resulted in greater toxicity (vomiting, stomatitis, and alopecia) which was less readily accepted. Tolerance of any of these regimens was unrelated to patient age, despite the belief that older women are less tolerant of chemotherapy. The earlier toxicity occurred, the greater was the number of subsequent courses associated with toxicity, and the lower was the total amount of drug received. The extent of the toxicity produced by the NSABP regimens and the end results obtained with them, must be compared with the end results and toxicity obtained by other regimens before making a choice of the adjuvant therapy to be used.
 ...
PMID:Acute toxicity during adjuvant chemotherapy for breast cancer: the National Surgical Adjuvant Breast and Bowel Project (NSABP) experience from 1717 patients receiving single and multiple agents. 701 22

We have previously demonstrated a dose response relationship in Hodgkin's disease for the combination of BCNU, VP16, Ara C and Melphalan, with the superior efficacy of the BEAM regimen requiring haemopoietic support, compared with miniBEAM. To further exploit this, we have attempted to escalate the VP16 dose in BEAM. The standard etoposide dose is 200 mg/m2 IV for four days. Thirty seven patients with refractory lymphoma received 400 mg/m2/day of etoposide, and 13 patients 600 mg/m2/day, in addition to BCNU, cytarabine, and melphalan. Toxicity and outcome parameters were compared in the preceding 40 patients, who received 200 mg/m2/day etoposide. The toxic mortality with 400 mg/m2/day of etoposide (3%) was identical to that for the standard BEAM regimen (5%). Two procedure related deaths occurred in the highest VP16 dose group (15%). The morbidity of the lower etoposide dose regimens was comparable, but 600 mg/m2/day induced significantly greater gastrointestinal toxicity. Twelve of the 13 patients receiving this dose suffered grade II-IV mucositis, with stomatitis, dysphagia and prolonged diarrhoea; 5 haemodynamically significant gastrointestinal haemorrhage, and 1 fatal toxic colitis. Granulocyte colony stimulating factor did not influence the nonhaematological toxicity. The three month response rates were similar (91%) in all dose cohorts. The maximum tolerable etoposide dose within the BEAM regimen is thus 400 mg/m2 for four days.
 ...
PMID:Dose intensification of etoposide in the BEAM ABMT protocol for malignant lymphoma. 858 Jul 95

Between January 1993 and December 1996, 21 children with advanced solid tumors were entered in a dose-escalating study of high-dose sequential chemotherapy followed by autologous stem cell transplantation. The diagnoses included neuroblastoma (NB) for 13 patients; Ewing's sarcoma (ES) for six patients and osteosarcoma for two patients. Nine patients received therapy as consolidation for primary metastatic disease, and 12 patients had had previous relapses. Treatment consisted of CY given i.v. at a dose of 7 g/m2 on day 1, followed by G-CSF until myeloid recovery. After 3 weeks of rest, all patients were given thiotepa i.v. on days 22-24. The total dose of thiotepa was 450 mg/m2 in three patients, 600 mg/m2 in six patients, and 750 mg/m2 in 12 patients. Melphalan was given i.v. at a dose of 180 mg/m2 i.v. on day 27 followed by stem cell infusion on day 28. Major toxic reactions included stomatitis, esophagitis, diarrhea and dermatitis. Three patients died of treatment-related complications. Twelve patients have had a relapse. Six patients (five with NB and one with ES) are alive in continuous remission 5-50 months (median 36) after transplantation. The results of this study show that it is feasible to administer high-dose sequential chemotherapy to children with advanced solid tumors.
 ...
PMID:High-dose sequential chemotherapy and autologous stem cell reinfusion in advanced pediatric solid tumors. 946 76

We evaluated the efficacy and safety of the conditioning regimen that consisted of TBI and melphalan (L-PAM), followed by hematopoietic SCT (HSCT) in 23 children with advanced hematological malignancies. The median age at HSCT was 9 (range, 2-15) years. The underlying diseases were ALL in 16 patients (5 in CR2, 3 in CR3, 6 in relapse (RP) and 2 in induction failure (IF)), AML in 4 patients (3 in RP and 1 in IF) and non-Hodgkin's lymphoma in 3 patients (1 in CR3, 1 in CR4 and 1 in RP). The stem cell sources were BM for 19 patients and cord blood for 4 patients. All patients received the conditioning regimen that consisted of TBI 12 or 13.2 Gy and L-PAM 210 mg/m(2). In all, 22 patients engrafted on the median of day 16 (range, 10-23). The regimen was well tolerated and common regimen-related toxicities (RRTs) included grade II stomatitis and grade I hepatic toxicity. The cumulative incidences of RP and TRM were 47.6 and 21.5%, respectively. At a median follow-up of 24.4 months, the probability of disease-free survival was 41.0%. The regimen may provide sufficient anti-leukemic effect without increased RRT for advanced pediatric hematological malignancies.
 ...
PMID:TBI and melphalan followed by allogeneic hematopoietic SCT in children with advanced hematological malignancies. 2104 10

Autologous stem cell transplantation (ASCT) after high-dose melphalan conditioning is considered a standard of care procedure for patients with multiple myeloma (MM). Current formulations of melphalan (eg, Alkeran for Injection [melphalan hydrochloride]; GlaxoSmithKline, Research Triangle Park, NC, USA) have marginal solubility and limited chemical stability upon reconstitution. Alkeran requires the use of propylene glycol as a co-solvent, which itself has been reported to cause such complications as metabolic/renal dysfunction and arrhythmias. EVOMELA (propylene glycol-free melphalan HCl; Spectrum Pharmaceuticals, Inc., Irvine, CA, USA) is a new i.v. melphalan formulation that incorporates Captisol (Ligand Pharmaceuticals, Inc., La Jolla, CA, USA), a specially modified cyclodextrin that improves the solubility and stability of melphalan and eliminates the need for propylene glycol. This new formulation has been shown to be bioequivalent to Alkeran. EVOMELA (200 mg/m(2)) was administered as 2 doses of 100 mg/m(2) each in a phase IIb, open-label, multicenter study to confirm its safety and efficacy as a high-dose conditioning regimen for patients with MM undergoing ASCT. At 5 centers, 61 patients (26 women) with a median age of 62 years (range, 32-73) were enrolled. All patients achieved myeloablation with a median time of 5 days post-ASCT, and all successfully achieved neutrophil and platelet engraftment with median times of 12 days post-ASCT and 13 days post-ASCT, respectively; treatment-related mortality on day 100 was 0%. Overall response rate (according to independent, blinded review) was high (100%), with an overall complete response rate of 21% (13% stringent complete response; 8% complete response) and overall partial response rate of 79% (61% very good partial response; 18% partial response). The incidence of grade 3 mucositis and stomatitis was low (10% and 5%, respectively) with no grade 4 mucositis or stomatitis reported (graded according to National Cancer Institute Common Terminology Criteria for Adverse Events). Based on investigators' assessment of mucositis using the World Health Organization (WHO) oral toxicity scale, 75% of patients had a shift in mucositis score from WHO grade 0 at baseline to a higher grade on study, of which 13% of patients reported WHO grade 3 as the worst post-treatment mucositis over the course of the study; there were no reports of WHO grade 4 mucositis during the study. This study confirms the efficacy and acceptable safety profile of EVOMELA, a new propylene glycol-free melphalan formulation, as a high-dose conditioning regimen for ASCT in patients with MM.
...
PMID:A Phase IIb, Multicenter, Open-Label, Safety, and Efficacy Study of High-Dose, Propylene Glycol-Free Melphalan Hydrochloride for Injection (EVOMELA) for Myeloablative Conditioning in Multiple Myeloma Patients Undergoing Autologous Transplantation. 2632 31