Outpatient high-dose chemotherapy with autologous stem-cell rescue for hematologic and nonhematologic malignancies.

PURPOSE: A prospective study to determine the feasibility of high-dose chemotherapy (HDC) and autologous stem-cell rescue (ASCR) in the outpatient setting. METHODS: One hundred thirteen consecutive patients underwent 165 cycles of HDC/ASCR for a variety of malignancies. HDC regimens were disease-specific. Initially, patients were hospitalized for HDC, discharged on completion, and maintained as outpatients unless toxicities required rehospitalization (subtotal outpatient transplantation [STOT]). Once this was established as safe, a total outpatient transplant (TOT) program was developed in which patients received all of the HDC, as well as supportive care, as outpatients. Patients who declined the outpatient programs received the same HDC and supportive care as inpatients. RESULTS: In 140 of 165 (85%) HDC cycles, patients agreed to participate in one of the outpatient transplant programs. Five patients in the STOT program could not be discharged from the hospital because of toxicities that developed during HDC; thus, 135 patients were monitored the outpatient setting, 95 (70%) of whom were never readmitted. The mean +/- SEM total hospital length of stay (LOS), including all readmissions and excess days after chemotherapy, was 18.33 +/- 5.06 days for patients who refused the outpatient program, 8.22 +/- 5.76 days for patients in the STOT program, and 2.81 +/- 7.66 days for those in the TOT program (P < .001). One treatment-related death occurred in each treatment setting: day 120 inpatient, day 17 STOT, and day 110 TOT. CONCLUSION: Outpatient management of HDC/ASCR is safe and acceptable for the vast majority of patients. The STOT program resulted in significant reduction in hospital LOS, while the TOT program appears equally safe and further reduces LOS. Hospitalization for HDC/ASCR is unnecessary in most patients.

Phase I clinical comparative study of monoclonal antibody KS1/4 and KS1/4-methotrexate immunconjugate in patients with non-small cell lung carcinoma.

A Phase Ia clinical trial was undertaken to evaluate and compare murine monoclonal antibody KS1/4 and KS1/4-methotrexate immunoconjugate in patients with Stage IIIB or IV non-small cell carcinoma of the lung. Six patients received KS1/4 alone and five patients received KS1/4-methotrexate conjugate. The maximal total dose received per patient in both groups was 1661 mg. Mild to moderate side effects in both groups included fever, chills, anorexia, nausea, vomiting, diarrhea, anemia, and brief transaminasemia. One patient who received antibody alone had an apparent acute immune complex-mediated reaction. Ten of 11 patients had a human anti-mouse response. Posttreatment carcinoma biopsies revealed binding of monoclonal antibody KS1/4 and deposition of C3d and C4c complement fragments. Monoclonal antibody binding and complement deposition correlated with increasing doses of infused antibody. There was one possible clinical response.

Alternating combination chemotherapy for stages III and IV ovarian carcinoma.

Thirty-nine previously untreated patients with stages III and IV ovarian carcinoma were treated with debulking surgery, followed by alternating combination chemotherapy with cisplatin, Adriamycin (Adria Laboratories, Columbus, Ohio), and cyclophosphamide (PAC); and hexamethylmelamine, cyclophosphamide, methotrexate, and 5-fluorouracil (HexaCAF). Of 19 patients with measureable disease at the onset of therapy, ten (53%) had at least a partial response to chemotherapy. Seven (18% of total) patients were found to be pathologically free of disease at secondlook surgery, but four patients relapsed 19 to 31 months after initiating therapy. The median progression-free survival period of all 39 patients entered into the study is 12 months, and the median crude survival is 21 months. The PAC/HexaCAF alternating combination chemotherapy regimen may be administered with moderate toxicity, but the treatment results are not superior to those reported for PAC or HexaCAF alone in advanced ovarian carcinoma.

Natural history of asymptomatic ulcerative plaques of the carotid bifurcation.

In 79 patients with 91 asymptomatic ulcerating lesions of the carotid bifurcation who were followed an average of 54 months, there were two strokes, one of which was preceded by a warning transient ischemic attack. These data suggest that asymptomatic type A and type B carotid ulcerating lesions do not carry a significant early risk of stroke and do not warrant prophylactic carotid endarterectomy. However, the effect of antiplatelet drugs and anticoagulation in enhancing the development of subintimal hemorrhagic lesions remains uncertain. Further data with serial follow-up, preferably by noninvasive means, will be necessary to define the evolution of asymptomatic ulcerating carotid plaques and eventually permit identification of those lesions that have significant stroke potential.

5-FU and allopurinol: toxicity modulation and phase II results in colon cancer.

Concurrent administration of allopurinol allows escalation of 5-FU doses in man when 5-FU is given by continuous infusion for 5 days. Forty-nine patients received 81 courses of treatment with 5-FU and allopurinol in phase I and II trials. The dose-limiting toxicity was mucositis; marrow toxicity was mild. Neurotoxicity, possibly related to 5-FU, occurred in eight patients. No responses were seen in 14 evaluable patients with colon cancer, 11 of whom had had prior 5-FU. One patient with Hodgkin's disease had a partial response; one patient with diffuse histiocytic lymphoma had transient disease regression. Although allopurinol does modify the toxicity of 5-FU, permitting dose escalation, it does not increase the therapeutic index in colon cancer. Infusional 5-FU deserves further study in lymphoma.

Valve competence following experimental venous valve autotransplantation.

In canine experiments, venous patency and valvular competence were evaluated following transposition of a valve-containing vein segment, with an without a distal arteriovenous (AV) fistula. The effects of distal fistula size on valvular function were also examined. Autogenous valve-containing venous segment grafts were placed in the femoral position. With no adjuncts, 90% of the grafts showed either occlusion, severe extrinsic narrowing, or intraluminal filling defects on early venograms, although 75% of valves were eventually competent at death. Veins that had undergone thrombosis and recanalization were routinely incompetent. With a distal AV fistula, all veins remained patent and 86% demonstrated valve competence. With both an AV fistula and dextran 40, all veins remained patent and all valves were component. Separately, graded size of AV fistulas did not result in loss of valve competence. Following venous segment transposition, continuous venous patency appears necessary for eventual valvular function, and this is enhanced by both a distal AV fistula and dextran.

Prognosis of asymptomatic ulcerating carotid lesions.

To determine the proper approach to asymptomatic carotid bifurcation ulcerated plaque (UP), 79 patients with 91 asymptomatic UPs were identified angiographically, and a 96% follow-up was obtained with a mean duration of three years. The cumulative stroke rate by life-table analysis was 1% at seven years. Sixty-three UPs in 55 patients were classified as small, and of these patients, transient ischemic attacks (TIAs) that were appropriate to the lesion developed in three and stroke in one (7% cumulative symptom rate). Twenty-four UPs in 21 patients were classified as large, and a TIA developed in one patient (9%), but no strokes were observed in this group. The cumulative mortality was 17% at three years and 52% at seven years. Life-table curves of several subgroups were compared and showed no significant differences in either stroke rate or mortality between any of these groups. On the basis of these data, and particularly the seven-year stroke rate of 1%, prophylactic carotid endarterectomy is not justified for asymptomatic carotid bifurcation ulcerations.

Regional differences in myocardial performance in the left ventricle of the dog.

To determine whether significant regional differences in shortening exist in the canine left ventricle, the shortening characteristics of small segments of the circumferentially oriented hoop axis fibers and the more longitudinally oriented fibers near the epicardium were examined using pairs of ultrasound crystals placed at three levels of the left ventricular free wall in the open-chest dog. Mean control shortening of the hoop axis fibers near the apex of the left ventricle averaged 20% of the end-diastolic length, significantly greater than shortening at the midventricular (13%) or basal (14%) levels. During transient periods of aortic constriction, end-diastolic length increased significantly and the extent of shortening was maintained for the hoop axis fibers at the apical and midventricular levels; end-diastolic length did not change and shortening decreased at the basal level. The epicardial fibers shortened an average of 5.6% of their end-diastolic length during control conditions at all three sites and showed small, parallel changes in shortening and end-diastolic length during aortic constriction. We conclude that significantly greater hoop axis shortening occurs near the apex of the left ventricle and that at this level a uniformly contracting model is inappropriate. In addition, the response of the hoop axis fibers to increased aortic impedance is not homogeneous, with a significant reduction in shortening occurring only at the base of the left ventricle where end-diastolic length does not increase.