Neo-adjuvant chemotherapy +/- immunotherapy with s.c. IL 2 in advanced squamous cell carcinoma of the head and neck: a pilot study

We carried out a pilot nonrandomized phase II study to compare the neo-adjuvant chemotherapic regimen with cisplatin, 5-FU and vinorelbine with the same combination plus s.c. IL 2 in advanced head and neck squamous cell carcinoma (HNSCC). The primary goals of the trial were to evaluate the feasibility and response rates of the two regimens. The study design consisted of a patient's assignment to either of the two following arms: Arm A: Cisplatin 80 mg/m2 i.v. on day 1; 5-FU 600 mg/m2 i.v. on days 2-5; and vinorelbine 20 mg/m2 i.v. on days 2 and 8, Arm B: the same chemotherapic regimen plus recombinant IL 2 (Proleukin, Eurocetus) 9 MIU s.c. daily from day 9 to 13 and from day 16 to 20 for every cycle. From March 1993 to November 1993 twenty three patients with Stage III-IV HNSCC were enrolled in the study. Patients could be evaluated for response to treatment if they had received at least 2 complete cycles of therapy. The overall response rate (ORR) was 63% in Arm A and 100% in Arm B. The differences for ORR and CR rates were statistically significant in favor of Arm B. The analysis for each of the three drugs included in the chemotherapy schedule shows that both the actually received average dose-intensity and the actually delivered average cumulative doses/patient were higher for Arm B (chemo-plus IL 2 therapy) (approximately 80% of programmed dose-intensity) than for Arm A (approximately 70% of programmed dose-intensity). Both the actually received average dose-intensity and the actually delivered average cumulative doses/patient for IL 2 were more than 80%. In both arms the most frequent side effects were myelosuppression, phlebitis and electrolyte disturbances. There were 2 toxic deaths, 1 in Arm A and 1 in Arm B, both for hematologic toxicity. Our "pilot" study suggests that the combination of cisplatin, 5-FU, vinorelbine plus IL 2 is a highly active, but rather toxic, neo-adjuvant treatment in advanced HNSCC with very high ORR and CR rates.     

A randomized cross-over study of high-dose metoclopramide plus dexamethasone versus granisetron plus dexamethasone in patients receiving chemotherapy with high-dose cisplatin

We carried out a randomized, single-blind, cross-over trial to compare the antiemetic effect, for both acute and delayed emesis, of granisetron plus dexamethasone (GRN+Dx) with that of high-dose metoclopramide plus dexamethasone (HDMP+Dx). Fifty-four patients with primary or metastatic lung cancer, given single-dose cisplatin (> 80 mg/m2) chemotherapy more than twice, were enrolled in this study. They were treated with both HDMP+Dx and GRN+Dx in two consecutive chemotherapy courses. On day 1, patients experienced a mean of 2.5 (SD = 4.3) and 0.1 (SD = 0.4) episodes of vomiting in the HDMP+Dx and the GRN+Dx groups, respectively (P = 0.0008). Complete response rate on day 1 was 45 and 90% in the HDMP+Dx and the GRN+Dx groups, respectively (P = 0.0001). Patients treated with GRN+Dx had a tendency to suffer more episodes of vomiting than the HDMP+Dx group on days 2-5, but it was not statistically significant. Twenty-four patients (57%) preferred the GRN+Dx treatment and 14 patients (33%), HDMP+Dx. In the HDMP+Dx group, nine patients (21%) had an extrapyramidal reaction, and 5 patients (12%) had constipation that lasted for at least two days. In contrast, no patients had extrapyramidal reactions, and 18 patients (43%) had constipation in the GRN+Dx group (P < 0.01). GRN+Dx was more effective than HDMP+Dx only in preventing the acute emesis induced by cisplatin. An effective treatment for delayed emesis is still needed.     

Immunotherapy and chemotherapy in children with neuroblastoma

Recent advances with immunotherapy in animal tumors suggested that trials with a combination of chemotherapy and immunotherapy in human malignant tumors might be worthwhile. A pilot program with Vibrio cholera neuraminidase-treated tumor cells plus BCG was tested in 3 patients who had had chemotherapy for disseminated neuroblastoma. Two of these children were in "complete remission" after radiation therapy and chemotherapy before the administration of immunotherapy. Relapse occurred in 5-6 months in all 3 patients. These disappointing results are discussed in relation to problems of current chemotherapy in disseminated neuroblastoma including results obtained at second-look operations in patients obtaining "complete remission."     

Skeletal and soft tissue sarcomas. Treatment with adjuvant immunotherapy

Because there is evidence for an active immunologic response against sarcoma, a clinical trial of adjuvant immunotherapy using bacillus Calmette-Guérin (BCG) and tumor cell vaccine was begun. Eleven of 18 patients with localized soft tissue sarcoma who received immunotherapy are free of disease, compared to only 5 of 15 treated by operation alone who are free of disease. Furthermore, immunotherapy also prolonged the median disease-free interval from 7.3 months to 15 months in the patients who experienced recurrence of their disease.     

Critical analysis of treatment of stage II and stage III melanoma patients with immunotherapy

Over the past 8 years, 244 patients with Stage II or III melanoma have been treated by cutaneous injection of a crude acellular homogenate of allogeneic melanoma cells (V-I) or a more concentrated fraction (V-II), followed in most patients by exchanges of WBC between paired partners. Patients with Stage III disease exhibited an overall response rate of 24% and prolongation of survival compared with control data. Stage II patients also had prolonged survival and reduced rate of recurrence over historic peers' data. Breakdown of subgroup data revealed that V-II plus exchange of WBC is similar to V-I plus exchange or V-II alone. However, recent experience of LTF suggests a higher response rate than in either V-I or V-II groups, particularly when autochthonous tumor is used for cross-immunization. The most meaningful immunologic data resulted from analysis of DNCB and MIF data. Patients negative to DNCB rarely respond to immunotherapy. A positive pretreatment MIF or positive conversion following treatment correlates with response, whereas, conversion of positive to negative predicts poor clinical performance.     

Cyclophosphamide and 4-Hydroxycyclophosphamide/aldophosphamide kinetics in patients receiving high-dose cyclophosphamide chemotherapy

Using a recently developed gas chromatography and mass spectrometry method to determine whole-blood cyclophosphamide (CP) and 4-hydroxycyclophosphamide/aldophosphamide (4-HO-CP/AP) concentrations, we investigated their pharmacokinetics in women receiving CP therapy. Patients (n = 18) received one or two courses of CP: (a) a 90-min i.v. infusion (4 g/m2) followed by a 96-h i.v. infusion (6 g/m2) in combination with high-dose thiotepa; or (b) a 96-h i.v. infusion (6 g/m2) in combination with high-dose thiotepa. Whole-blood exposures to CP [area under the whole blood concentration versus time curve (AUCCP)] and 4-HO-CP/AP (AUC4HOCP) between courses 1 and 2 were compared after normalization to dose (g/m2). A nonproportional increase was observed for the AUCCP between the first course [1112 micrometer. h/g/m2 +/- 14% coefficient of variation (CV)] and the second course (1579 micrometer . h/g/m2 +/- 28% CV) (P < 0.001). In contrast, the AUC4HOCP (27 micrometer . h/g/m2 +/- 25% CV) determined for the first course was 29% higher than the AUC4HOCP (21 micrometer . h/g/m2 +/- 26% CV) for the second course (P < 0.01). The interpatient whole-blood exposures to both CP and 4-HO-CP/AP were remarkably consistent in this patient population with percent CVs ranging from 14 to 28%. Because thiotepa (800 mg/m2) was administered simultaneously with CP during the second course of treatment, possible inhibition of CP metabolism by thiotepa was investigated using human liver microsomes in vitro. IC50 values determined for inhibition of CP metabolism in three individual liver donors ranged from 1.0 to 40 micrometer. However, the clinical relevance of this observation has not been established.     

Articulation in children with Down's syndrome. A pilot study

The articulation of children with Down's syndrome (trisomie 21, T21) in comparison to a group of age-matched normal probands was investigated in a clinical study, using digital sonagraphics (recording of frequency, amplitude and time of the speech signal), with peripheral factors taken into consideration. The T21-Group (n = 10) revealed a higher variability as well as a longer articulation of the test word "Tasse" than the Control Group (n = 10). There was no clear-cut dependence of speed and quality of articulation on all of the peripheral factors evaluated (Angle Class, overbite, oral motor ability, hearing disorder, logopedics, Castillo-Morales stimulating plate treatment). The results of our investigation show differing patterns of articulation in T21 children compared with normal probands, using a reproducible method. A clear-cut influence of various influencing peripheral factors as reported in the literature could not be found for the T21-Group. Thus, central factors seem to have a great impact on articulation in T21 patients.     

Port-site metastases. A prospective study of 131 cases

Laparoscopic staging and laparoscopic treatment of gastrointestinal malignancy is still controversial because some studies report port-site metastases. BACKGROUND: The aim of the study is to determine in 131 patients, with prospective follow-up, after laparoscopic staging or laparoscopic treatment the incidence of port-site metastases. METHODS: 131 patients, with gastro intestinal malignancy, proved or with peritoneal carcinomatis or liver metastases, were included. In 57 cases only laparoscopic staging is performed in 49 cases laparotomic treatment is performed a after laparoscopic staging; in 57 cases (43.5 per cent) tumor invaded serosa. RESULTS: The median follow-up was 17.7 months (3 to 62 months). 502 port-sites were controlled. One patient (0.7%) has presented one port site metastasis 3 months after right colectomy for carcinoma with local carcinomatis. CONCLUSION: The study affirm that port-site metastases are rare. They are favorised by serosa invasion. The low rate indulge in laparoscopic staging to recognize occults lesions which are not detected by conventionals examinations in 44.2 per cent in this study.     

Motivational interviewing with cocaine-dependent patients: A pilot study.

A brief motivational interviewing (MI) intervention was evaluated within the context of an outpatient, cocaine-detoxification program. MI was hypothesized to assist patients in completing the detoxification program and to improve outcomes during subsequent treatment. Participants (N = 105) were randomly assigned to MI or to detox-only conditions. Results indicated that although participants completed the detoxification program at equal rates, completers who received MI increased use of behavioral coping strategies and had fewer cocaine-positive urine samples on beginning the primary treatment. MI patients with lower initial motivation were more likely to complete detoxification. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Results of a pilot study with high-dose medroxyprogesterone acetate in the treatment of metastasizing breast carcinoma

Nineteen patients with advanced breast cancer were treated with 1 g medroxyprogesterone acetate (MPA) i.m. daily for 4 weeks. The therapy was well tolerated. The measurable tumor lesions showed a regression of more than 50% in 6 cases; the mean duration of remission was 12 months. In 12 patients the treatment led to a marked subjective improvement. On the basis of these data the authors feel that high-dosage MPA warrants further investigation in the treatment of metastatic breast cancer.     

Treatment of septic shock with immunotherapy

Sepsis is the thirteenth leading cause of death in the United States. Despite increased knowledge about its pathophysiology, availability of powerful antibiotics, and advanced diagnostic and monitoring techniques, mortality rates have not changed significantly over the past 30 years. Immunotherapy may improve outcome in the critically ill with sepsis, although trial results have been disappointing to date.     

Treatment of refractory depression with high-dose thyroxine

In an open clinical trial we investigated whether addition of supraphysiological doses of thyroxine (T4) to conventional antidepressant drugs has an antidepressant effect in therapy-resistant depressed patients. Seventeen severely ill, therapy-resistant, euthyroid patients with major depression (12 bipolar, five unipolar) were studied. The patients had been depressed for a mean of 11.5 +/- 13.8 months, despite treatment with antidepressants and, in most cases, augmentation with lithium, carbamazepine, and neuroleptics. Thyroxine was added to their antidepressant medication, and the doses were increased to a mean of 482 +/- 72 micrograms/day. The patients' scores on the Hamilton rating Scale for Depression (HRSD) declined from 26.6 +/- 4.7 prior to the addition of T4 to 11.6 +/- 6.8 at the end of week 8. Eight patients fulfilled the criteria for full remission (a 50% reduction in HRSD score and a final score of < or = 9) within 8 weeks and two others fully remitted within 12 weeks. Seven patients did not remit. The 10 remitted patients were maintained on high-dose T4 and followed up for a mean of 27.2 +/- 22.0 months. Seven of these 10 remitted patients had an excellent outcome, two had milder and shorter episodes during T4 augmentation treatment, and one failed to profit from T4 treatment during the follow-up period. Side effects were surprisingly mild, and no complications were observed at all. In conclusion, augmentation of conventional antidepressants with high-dose T4 proved to have excellent antidepressant effects in approximately 50% of severely therapy-resistant depressed patients.     

Modeling techniques, drug-abstinence behavior, and heroin addicts: A pilot study.

Investigated the applicability of a "vicarious behavior induction" (VBI) strategy to a residential treatment program for heroin addicts. This strategy was tested using a "videomodel" procedure, in which Ss viewed a series of videotapes developed to depict a model exhibiting "coping" behavior in solving problems related to maintaining drug abstinence (i.e., accepting help, job interviewing, capitalizing on street skills). These results were compared to those obtained from Ss who had viewed a videotaped lecture about coping behavior ("videolecture"). 22 Black heroin addicts from an urban community-based residential drug-abuse treatment program were randomly assigned to either a videomodel or videolecture group. In small subgroups they discussed their respective videotapes with an ex-addict paraprofessional and the E. Ss who participated in the videomodeling group had substantially better vocational outcomes 30, 90 and 180 days after treatment than those who participated in the videolecture group. Advantages of the VBI behavior change strategy are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A proper sequence for the treatment of B16 melanoma: chemotherapy, surgery, and immunotherapy

The therapeutic effectiveness of surgery, chemotherapy, and immunotherapy alone and in combination were studied in the B16 melanoma model. The sequence of chemotherapy and immunotherapy as adjuvants to surgery proved important: Chemotherapy was significantly better when given before surgery; immunotherapy was more effective when delivered after surgery. The most effective therapeutic regimen was a combination of all three modalities: a single course of chemotherapy preceding surgery followed by immunotherapy.     

A prospective safety-monitoring study of immunotherapy with biologically standardized extracts

We evaluated the safety of immunotherapy in 419 patients who attended our allergy department for treatment. They were suffering from rhinitis and asthma caused by sensitization to grass pollen or Dermatophagoides pteronyssinus. Immunotherapy was given by biologically standardized aluminum hydroxide adsorbed extracts according to a conventional schedule. Local reactions were recorded in 10.5% of the patients and systemic reactions in 4.8%. Only 0.37% of the doses administered were associated with systemic side-effects. We found that 84% of the patients who showed systemic reactions were asthmatic subjects (P < 0.01), and most of them were sensitized to D. pteronyssinus (71%). Side-effects occurred more frequently during the dose-increase period (P < 0.05). After 9482 doses had been administered, no anaphylactic shock or life-threatening reactions were registered. We believe the risk associated with immunotherapy to be drastically reduced when treatment is carefully monitored by skilled personnel. In such conditions, as shown by our study, immunotherapy is safe.     

Methotrexate treatment of ectopic pregnancy. A pilot study

The incidence of ectopic pregnancy is rising but the clinical presentation of the disease has changed simultaneously. Nowadays, the majority of ectopic pregnancies are diagnosed before rupture. This stimulated us to attempt methotrexate therapy (1 mg/kg body weight injected locally or 50 mg given orally) in 12 cases verified by transvaginal ultrasound and presenting with increasing beta-hCG values. The treatment proved successful in 67% of the cases, even though high levels of beta-hCG and foetal heart activity were accepted as inclusion criteria. Eight patients later achieved intrauterine pregnancies, and seven healthy babies were delivered. Randomized, controlled studies are needed.     

Health promotion for women with physical disabilities: A pilot study.

Objective: To pilot test a health promotion intervention for women with physical disabilities. Design: Pre- and postintervention questionnaires. Participants: Two groups of women with physical disabilities (n=15). Intervention: Seven-session weekly workshop intervention grounded primarily in social-cognitive theory. Setting: Disability and rehabilitation settings. Main Outcome Measures: Indicators of health status. Results: Statistically significant positive changes between pre- and postintervention scores on measures of self-efficacy for dietary behaviors, medical decision making, social interaction, physical functioning, impact of physical limitation on role activities, and vitality. Conclusion: Women with disabilities who participate in this health promotion intervention may exhibit improvements on indicators of health status. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Adolescents and sexuality in family practice. A pilot study

It is well established that teenagers are generally dissatisfied with the sexual education they receive from school and parents. While several alternative sources of sex counselling have been suggested (i.e. an anonymous and semi-official telephone hot-line), the role of the general practitioner in sexual guidance of youngsters is only poorly evaluated. One hundred and sixty-eight teenage callers of "The Adolescent Sexuality Hot-line" were asked about their experience with sexual counselling by their family doctor. One third had actually discussed such topics with their g.p., and a total of 44.6% (significantly more girls than boys) regarded their g.p. as a desirable interlocutor on these issues. The reasons for having approached a g.p. for counselling differed according to gender, as did the causes for not wanting to involve a g.p. in sexual matters: boys tended to state shyness and lack of anonymity as main causes, whereas girls more often pointed to personal aspects of the doctor.     

Behavior rehearsal and social competence: A pilot study.

Investigated the effects on socially incompetent college students of a group program that used social-learning theory and behavior-rehearsal techniques. 20 students referred from a university mental health clinic were assigned to 1 of 2 treatment groups (Groups 1 and 2) or a control group (Group 3). Groups 1 and 2 participated in 8, 2-hr sessions involving behavior-rehearsal and modeling procedures, whereas Group 3 was given readings on social skills and assertiveness training. All groups were given pretests, posttests, and follow-up tests on Forms A and B of the 16 PF. Data were analyzed with a repeated measures analysis of variance. Significant gains in social competence were shown by Groups 1 and 2 on the posttest and the follow-up test. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Successful management of stage 4S neuroblastoma and severe hepatomegaly using absorbable mesh in an infant

This report describes the use of an absorbable mesh in an infant with stage 4S neuroblastoma who required decompressive laparotomy. At the time of laparotomy, a SILASTIC silo was placed. After 12 days, the liver had not reduced in size despite chemotherapy and radiation therapy. Because of concern for infection, the silo was removed, and an absorbable polygalactin (Vicryl) mesh was placed. Wet-to-dry dressings were used to manage the mesh. A granulation base developed that provided a physiological closure of the abdominal cavity. Forty-two days after placement of the absorbable mesh, the liver had reduced to a size that permitted mobilization of skin flaps for a surgical abdominal closure. The liver continued to reduce in size, allowing the fascial edges to draw together. The patient is now 2 years old with no signs of residual tumor or ventral hernia.