We carried out an open, non‐randomized phase II study including all patients treated with whatever chemotherapy or combined modality regimen for whatever cancer who were in clinical objective ...response (complete response, CR, or partial response, PR) or stable disease (SD). The treatment consisted of administration of recombinant interleukin‐2 (rIL‐2) at a dose of 1.8 MIU subcutaneously three times/week (every other day) for the first 2 weeks of every month plus medroxyprogesterone acetate (MPA) 500 mg/day every other day plus antioxidant agents alpha‐lipoic acid 300 mg/day and N‐acetyl cysteine 1800 mg/day or carbocysteine lysine salt oral solution 2.7 g/day. The treatment was admin‐ istered for 1 year except when progression of disease occurred. The primary study endpoints were to define clinical outcome, i.e. duration of response, survival (overall survival, OS and progression‐free survival, PFS), the toxicity profile, and the evaluation of quality of life (QL). As secondary endpoints, we measured the changes of lymphocyte count, serum levels of proinflammatory cytokines, IL‐2, C‐reactive protein (CRP) and leptin, blood levels of reactive oxygen species (ROS) and antioxidant enzymes (glutathione peroxidase, GPx and superoxide dismertase, SOD). From July 1998 to June 2003, 42 patients were enrolled in the study (M/F ratio, 39/3; mean age, 62.5 years). Twenty (47.6%) patients were elderly (>65 years). The majority of patients had either head and neck cancer or lung cancer, 88% had locally advanced or metastatic disease at diagnosis, and 76% had ECOG 0. Forty patients were previously treated with chemotherapy (27 also with radiotherapy), two with IL‐2 and interfiron (IFN), one with endocrine therapy and one with only surgery. We obtained an objective response to maintenance treatment of 50%. Median duration of response was 19 months and median PFS was 33 months. Median duration of maintenance treatment was 12 months, median follow‐up duration from diagnosis to June 2003 was 40 months, and median follow‐up duration from study entry to June 2003 was 17 months. The median overall survival has not been reached. Toxicity was negligible. As for QL, a significant improvement of cognitive functions was observed, whereas all other functioning and symptom scales did not change significantly. As for laboratory parameters, absolute lymphocyte count increased significantly, IL‐6, IL‐1β, tumor necrosis factor‐α, CRP, and fibrinogen decreased significantly whereas IL‐2 and leptin increased significantly after treatment. ROS decreased significantly, whereas GPx increased significantly after treatment. Patients alive at study end showed a significant increase in absolute lymphocyte count, IL‐2, leptin, and GPx and a significant decrease of proinflammatory cytokines, CRP, fibrinogen, and ROS, whereas patients who died before study end exhibited only a significant increase in absolute lymphocyte count, IL‐2, and GPx and a significant decrease of ROS. Long‐term combined maintenance therapy with rIL‐2 + MPA + antioxidant agents is feasible, has a very low toxicity, and results in the improvement of clinical outcome, QL, and laboratory parameters.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The purpose of the study was to assess response rate, clinical outcome, organ/function preservation and toxicity in head and neck cancer patients treated with induction chemotherapy followed by ...concomitant chemoradiotherapy and, when necessary, limited surgery. The study was a phase II non-randomized trial. Induction chemotherapy consisted of 6 weekly doses of carboplatin at AUC of 2 and docetaxel 30 mg/m(2) (1 h) followed by 5 cycles of docetaxel 25 mg/m(2)/day 1, 5-FU 600 mg/m(2) c.i. days 1-5, hydroxyurea 500 mg orally every 12 h for 11 and concomitant twice daily radiation therapy at 150 cGy/fraction given every other week per 5 cycles (TFHX), for a total radiation dose of 75 Gy. 13 cis-retinoic acid was administered for chemoprevention and systematic prophylaxis of mucositis with systemic amifostine and local GM-CSF was administered to all patients during TFHX. Conservative surgical resection was reserved to patients with no optimal response (PR > or =70%), whereas radical surgery was performed as salvage treatment. Thirteen patients (mean age 54.9 years, range 44-62; 12/13 site oropharynx, all stage IV) were enrolled: 31% of patients had ECOG performance status (PS) 0 and 69% had PS 1. Response to induction chemotherapy was analyzed in 12 patients: 2/12 (16.7%) achieved a partial response (PR) for an overall response (ORR) of 16.7%, 10/12 (83.3%) achieved stable disease (SD). TFHX was administered to 7 patients: 2 patients (28.6%) had complete remission (CR), 1 patient (14.3%) had PR for an ORR of 42.9%, 3 patients (42.8%) had SD and 1 patient (14.3%) had PD. At the completion of TFHX, 1 patient underwent local therapy. The toxicity was mild and consisted in: grade 3/4 neutropenia (7.7%), anemia (23.1%), diarrhea (15.4%), mucositis (7.7%), neurotoxicity (7.7%) during induction chemotherapy. During TFHX only 42.8% of grade 3/4 mucositis was observed. All patients spared organ/function. In conclusion, this regimen has been found feasible for its acceptable toxicity, particularly mucositis. However, the overall response rate and the data on survival were not satisfactory.
An open, non-randomized phase II study was carried out including patients with advanced solid tumors who achieved an objective response or disease stabilization as a result of previous chemotherapy, ...to receive a maintenance treatment with recombinant interleukin-2 (rIL-2) plus medroxyprogesterone acetate (MPA) plus antioxidant agents alpha-lipoic acid (ALA) and N-acetyl cysteine (NAC). The first study endpoints were to define clinical outcome and toxicity as well as the evaluation of quality of life. As secondary endpoints we measured the changes of lymphocyte absolute count, the serum levels of proinflammatory cytokines, IL-2, C-reactive protein (CRP) and leptin after treatment. rIL-2 was administered at a dose of 1.8 MIU subcutaneously 3 times/week on alternate days for the first two weeks of every month and MPA was given orally at a dose of 500 mg/day at alternate days without interruption. ALA 300 mg/day orally and NAC 1800 mg/day orally were also administered continuously. Twenty-eight patients were enrolled in the study. The median duration of maintenance treatment was 10 months (6-30+). The response to maintenance treatment at September 15, 2001 was: CR 11 patients (39.3%); SD 2 patients (7.1%); PD 15 patients (53.6%). The median duration of response was 11 months (6-34+). The median follow-up duration was 11 months (6-34+). The median OS was not reached. The median PFS was 21.5 months (1-40+). The 1-year survival rate was 72.2%. At September 15, 2001, 16 patients were still surviving. No grade 3/4 toxicity and one grade 2 skin toxicity were observed. We found a significant increase of the absolute lymphocyte count and serum levels of IL-2 and a significant decrease of TNF alpha after treatment. The evaluation of patient subgroups showed the following: the patients alive at the end of study had a significant increase of lymphocyte count, IL-2 and leptin, and a significant decrease of IL-1 beta, IL-6 and TNF alpha, whereas the patients who had died had only a significant increase of lymphocyte count and IL-2. Among the patients alive, those in objective clinical response (CR + PR) + those in SD had a significant increase of lymphocyte count, IL-2 and leptin and a significant decrease of IL-1 beta, IL-6 and TNFalpha, whereas those with PD had no significant changes in any of the above values. We conclude that the combination of s.c. rIL-2 with oral MPA and anti-oxidant agents ALA and NAC in an intermittent schedule, repeated for a long-term period, is feasible, has a very low toxicity and results in the improvement of biological markers which are predictive for patient outcome.
The aim of this study was to assess the impact of three different psychological interventions on the quality of life (QL) of elderly cancer patients with symptoms of anxiety and/or depression. ...Seventy‐four patients were enrolled in the study. All were aged over 65 and had solid tumours or haematological malignancies, generally in advanced stages (III‐IV). The cancer treatment was administered for a mean duration of 5 months and the mean number of chemotherapy cycles was 4. After stratification for the main prognostic factors, patients were randomly assigned to one of three groups: Group A, psychopharmacological treatment; Group B, treatment A plus social support carried out by volunteers and Group C, treatment as Group B plus structured psychotherapy. The planned duration of intervention was the same as that of the medical treatment. Patients who did not complete the planned chemotherapy nevertheless received all the planned psychological intervention. The evaluation of patients' QL was assessed using either uni‐ or multi‐dimensional instruments to explore functional status and physical symptoms as well as psychological status at subsequent times during treatment (i.e., pre‐treatment, mid‐treatment and at the end of treatment). The present study shows that the combination of psychopharmacological treatment with either social support for patients and their relatives carried out by volunteers (SSV), or SSV plus structured psychotherapy (SSV + SP), yielded the best results in terms of QL in the long‐term treatment of elderly patients with advanced cancer. According to the analysis these two ‘integrated’ approaches proved to be almost equally effective.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Our study belongs to the clinical trials in which the health-related quality of life (HQL) evaluation constitutes the primary endpoint. It was carried out with the aim of comparing the impact of ...three different types of psychological intervention, namely a psychopharmacological treatment alone, the same treatment plus social support carried out by volunteers (SSV) and a third treatment modality including "structured psychotherapy" (autogenous training), on improving the HQL of elderly cancer patients undergoing antineoplastic therapy with symptoms of anxiety and/or depression related to their disease. The eight questionnaires used for HQL evaluation were generally self-rated and multidimensional but unidimensional models were also employed. Seventy-four patients aged over 65 years with either solid tumors in different sites or hematological malignancies, generally in advanced stages (III-IV), were enrolled in the study. Of these patients, 72 (42 men and 30 women, mean age 70.68 years, range 66-85) were evaluable. Our study highlighted the usefulness of the pharmacological therapy (alprazolam + sulpiride) and of other specific ancillary treatments in reducing the incidence of the main HQL-related side-effects of antineoplastic therapy and the superiority of an "integrated" strategy, based both on psychopharmacology and psychosocial interventions, such as SSV with or without structured psychotherapy. The one-way analysis of variance carried out by us did not allow us to draw definitive conclusions about which of the two integrated treatments was to be considered the treatment of choice, as they proved to be almost equally effective.
We report the case of a 52-year-old woman with primary CD30+ anaplastic large-cell lymphoma of T cell phenotype with skin involvement, stage IVB, fulfilling almost all the clinical, histopathologic ...and immunophenotypic criteria for this disease, associated with adult-onset celiac disease. The diagnoses of malignancy and celiac disease were made during the same clinical episode. The clinical course of the patient has been extremely favorable and she is in complete remission, 15 months after finishing consolidation therapy.
The aim of the investigation was to study directly the IL-2 receptor (IL-2R) and its subunits, p55 and p75 chains, either membrane-bound or soluble, on PBMC of patients with solid malignancies and, ...indirectly, the same patients' PBMC ability to produce IL-2. Fifty-eight cancer patients, 29 men and 29 women, were studied: their mean age was 57.3 yr, range 35-79. Twenty-two healthy age-sex-matched subjects served as controls. The tumors were the most common and the most representative among human cancers, i.e., breast, lung, head and neck, digestive tract and liver, prostate and gynecologic cancers: they were generally in advanced stages and in 23 cases metastatic. The PBMC proliferative response to PHA, PHA plus IL-2, and IL-2 was evaluated along with the response to PHA in the presence of anti-p55, anti-p75 monoclonal antibodies, or both. Moreover, membrane-bound IL-2R (p55 and p75 chains) on PHA-stimulated PBMC was detected, along with soluble IL-2R in the serum and in the culture supernatants. The conclusions suggest that in solid malignancies: the membrane-bound IL-2Rs, both p55 and p75 chains, are expressed normally, there is an high serum level of soluble IL-2R, there is a normal release of soluble IL-2R in culture, and there is an indirect evidence of a lack of IL-2 production. Therefore, no primary impairment of IL-2R was found in solid tumors. Moreover, in our study we have found no difference in any parameter studied between patients with and patients without metastases.
Cancer-related anorexia-cachexia syndrome (CACS) is a complex syndrome characterised by progressive weight loss with depletion of host reserves of skeletal muscle and, to a lesser extent, adipose ...tissue, anorexia, reduced food intake, poor performance status and quality of life that often precedes death 1. At the time of diagnosis, 80% of patients with upper gastrointestinal cancers and 60% with lung cancer have already experienced substantial weight loss 2. The prevalence of cachexia increases from 50 to > 80% before death and in > 20% cachexia is the main cause of death 2. CACS results from the interaction of the host and the tumour. However, its nature is incompletely understood 3 6, including the dynamics of host response (activation of systemic inflammatory response, metabolic, immune and neuroendocrine changes) and those tumour characteristics or tumour-derived products that influence expression of the syndrome (e.g. proteolysis-inducing factor, PIF).
