SEARCH · Search PubMed

Results for “ASTHENIA”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 955 records · Page 53Linked to original sources

PubMed2006

[DRESS syndrome related to Hexaquine (quinine and thiamine)].

BACKGROUND: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS syndrome) is a severe drug eruption defined as an association of a drug reaction, mostly cutaneous, laboratory abnormalities with the presence of hypereosinophilia and/or atypical lymphocytes, and involvement of one or more organs. We report a case of DRESS syndrome associated with quinine or thiamine (which in France are combined in Hexaquine with serious hepatitis and renal failure and associated viral reactivation of Human Herpes Virus 6 (HHV6). OBSERVATION: A twenty-three year-old woman was hospitalized for asthenia, fever, erythroderma, facial edema and painful cervical lymph nodes. Laboratory results showed inflammatory syndrome, hypogammaglobulinemia and the presence of activated atypical lymphocytes. Broad screening for infectious serology showed HHV6 reactivation with marked increase in specific IgG levels within two weeks and detection of circulating DNA in blood by PCR (polymerase chain reaction). Two severe complications subsequently appeared: cytolytic hepatitis and interstitial nephritis. The outcome was favorable with oral corticosteroid therapy. Repeated history-taking did not initially identify any causal agent, but several weeks later, the patient remembered taking Hexaquine (quinine and thiamine) for essential muscular cramps daily for 27 days before the onset of symptoms. The patient had taken no other medication during the previous weeks. One year later, at the end of an enteroviral infection, a skin rash similar to the first episode was seen but in isolation on this occasion, suggesting minor reactivation of DRESS syndrome. DISCUSSION: To our knowledge, ours is the first reported case of DRESS syndrome associated with this drug. Because of the difficulty of identifying the causative drug, even though taken alone, our case once again illustrates the importance of spending adequate time on history taking. Although the physiopathology of DRESS syndrome has not yet been fully elucidated, it is nevertheless probable that it is a multi-factor phenomenon (involving medication and viruses among others).

Adult↗

PubMed2002

Depression induced by treatment with interferon-alpha in patients affected by hepatitis C virus.

BACKGROUND: Several studies found a high incidence rate of neuro-psychiatric complications during long-term therapy with interferon alpha (IFNalpha), e.g. slowness, severe fatigue, hypersomnia, lethargy, depressed mood, mnemonic troubles, irritability, short temper, emotional lability, social withdrawal, and lack of concentration. The aim of this study was to examine the incidence of depressed mood and major depression in patients who were treated with IFNalpha. METHODS: 30 patients, affected by chronic active C-hepatitis, have been evaluated at baseline and 3 months after IFNalpha treatment. The evaluation consisted of psychometric assessments employing the DSM-IV criteria and the Montgomery Asberg Depression Rating Scale (MADRS). RESULTS: At end-point, 40.7% of the patients suffered from a full blown major depression, according to the DSM-IV criteria for major depression. IFNalpha treatment induced a significant increase in the MADRS score from baseline to 3 months later. The MADRS items which were significantly increased at end-point were: expressed and unexpressed sadness; irritability; insomnia; loss of appetite; and asthenia. DISCUSSION: The results show that prolonged IFNalpha treatment may induce depressive symptoms and major depression in a considerable number of subjects.

Affect↗

PubMed1997

Luciani's work on the cerebellum a century later.

In 1891, Luigi Luciani published his famous monograph on the cerebellum and formulated his triad of the cerebellar symptoms: atonia, asthenia and astasia, which explained all troubles provoked by cerebellar lesions; later he added a fourth sign, dysmetria. In spite of the fact that it was advanced in a pre-electrophysiological period, Luciani's interpretation of the cerebellar role in many motor functions survives more than a century later and his terminology has entered the routine of the neurological examination. With the modern knowledge of cerebellar circuitries, we can state that Luciani rightly pointed out the role of the cerebellum in regulating postural tone and muscular force, and that conversely he was wrong in denying cerebellar influence in co-ordination of multi-joint movements and the somatotopic localizations in the cerebellar cortex and nuclei. In spite of this, Luciani's work represents a milestone in cerebellar physiology.

Cerebellum↗

PubMed2000

The effects of chronic, sustained-release moxonidine therapy on clinical and neurohumoral status in patients with heart failure.

AIMS: Congestive heart failure (CHF) is characterized by elevated plasma norepinephrine (PNE) associated with a poor prognosis. Moxonidine selectively stimulates medullary imidazoline receptors which centrally inhibit sympathetic outflow and potently suppress levels of circulating PNE. This study was designed to evaluate the effects of central sympathetic inhibition on clinical and neurohumoral status in patients with CHF. METHODS AND RESULTS: This study evaluated 25 patients (age=69+/-7 years, 20 males) with symptomatic CHF (NYHA II-III), stabilized on standard therapy. The mean ejection fraction was 28+/-7% at baseline. Patients were titrated in a double-blind fashion to 11 weeks of oral therapy with placebo (n=9) or sustained-release (SR) moxonidine 0.9 mg bid (n=16). Clinical and neurohumoral status were evaluated at baseline, on chronic therapy at the target dose, and during cessation of therapy. All patients completed the trial and reached the target dose. Dry mouth, symptomatic hypotension, and asthenia were more frequent in the moxonidine SR-treated group. PNE was substantially reduced after 6 weeks at the maximum dose (0.9 mg bid) by 50% vs. placebo (P<0. 0005). A reduction in 24-h mean heart rate (P<0.01) was correlated to the reduction in PNE (r=0.70, P<0.05). A 36% increase in the standard deviation of normal-to-normal intervals (SDNN) was observed in the moxonidine SR group vs. a 2% decrease for placebo (P=0.06); for the root mean square of successive differences (rMSSD), there was a 21% increase for moxonidine SR vs. a 19% decrease for placebo (P<0.05). Abrupt cessation of chronic therapy resulted in substantial increases in PNE, blood pressure, and heart rate. CONCLUSIONS: Chronic therapy with a sustained-release formulation of moxonidine in patients with CHF was well tolerated, with substantial and sustained reductions in PNE. The tachyarrhythmias were attenuated, with evidence of improved autonomic tone. Due to the observed effects following moxonidine discontinuation, tapering of therapy is recommended.

Blood Pressure↗

PubMed2002

Origin of symptoms in patients with cachexia with special reference to weakness and shortness of breath.

Cachexia is a complication of many disorders. It is associated with an extremely poor prognosis and many symptoms. The wasting process affects particularly skeletal muscle causing extreme fatigue and weakness. In many underlying conditions associated with cachexia, the patient also suffers an often unexplained severe dyspnoea along with weakness, asthenia and exhaustion. There appears to be marked similarities in the cause of dyspnoea and fatigue between different cachectic conditions. Using the example of cardiac cachexia, this article reviews the evidence linking skeletal muscle reflex inputs to ventilatory control and exaggerated chemoreflex responses as candidates for the heightened perception of dyspnoea which cannot be explained by heart or lung dysfunction in many patients. Evidence is reviewed that similar processes may occur in other cachexias, especially those complicating cancer, AIDS, chronic liver disease, and chronic lung disease. Potential novel therapeutic strategies to combat these cachexia symptoms are reviewed.

Cachexia↗

PubMed2000

Phase II study of docetaxel in the treatment of patients with advanced non-small cell lung cancer in routine daily practice.

The purpose of this study was to evaluate the efficacy and safety of docetaxel as first- and second-line chemotherapy for advanced non-small cell lung cancer (NSCLC) under routine clinical conditions. Two hundred and three patients with advanced NSCLC received docetaxel 100 mg/m2 (1-h intravenous infusion) every 3 weeks, with oral corticosteroid pre-medication, of whom 173 were eligible. Median age was 60 (29-78) years and median Karnofsky performance status was 80% (60-100). A total of 77% of patients had metastatic disease, 33% had bone metastases and 18% had liver metastases. The treatment was second-line or more for 72 patients (35%). Overall response rates in the eligible population were 19.7% [95% CI, 12.5-23.0] for both treatments, 22.6% for first-line treatment and 13.8% for second-line treatment. Median survival was 8.3 months and 1-year survival was 35% for the overall population (8.7 months and 38%, respectively, for patients receiving first-line treatment and 7.2 months and 27%, respectively, for patients receiving second-line treatment). Neutropenia, grade 3 and 4, occurred in 57% of the cycles and 5% of patients experienced febrile neutropenia. Alopecia (62% of patients), neuro-sensory symptoms (32%), asthenia (28%), diarrhea (22%), nausea (22%) and nail disorders (20%) were the most common non-hematological adverse effects. A total of 33% of patients suffered fluid retention, despite the use of corticosteroid pre-medication, but this was only severe in 1.5% of patients. It was possible to confirm the efficacy of docetaxel as a single agent for first- and second-line chemotherapy in a large patient population treated in a community setting.

Adult↗

PubMed2001

Docetaxel in combination with gemcitabine plus rhG-CSF support as second-line treatment in non-small cell lung cancer. A multicenter phase II study.

BACKGROUND: Docetaxel in combination with gemcitabine is an active front-line chemotherapy regimen against non-small cell lung cancer (NSCLC) with acceptable toxicity. A multicenter phase II study was conducted in order to determine the toxicity and efficacy of this combination, as salvage treatment in patients progressing after a cisplatin-based front line regimens. PATIENTS AND METHODS: Thirty-two patients with histologically confirmed, bidimensionally measurable NSCLC, who failed prior cisplatin-based chemotherapy were enrolled. The patients' median age was 62.5 years, 29 (91%) were male, 23 (72%) had disease stage IV, and 22 (69%) had a performance status (WHO) 0-1. Gemcitabine (900 mg/m(2)) was administered on days 1 and 8 and docetaxel (100 mg/m(2)) on day 8, after appropriate premedication. rhG-CSF (150 microg/m(2)) was given prophylactically from day 9 to 15. Treatment was repeated on an outpatient basis every three weeks. RESULTS: A total of 127 chemotherapy cycles were administered. In an intention-to-treat analysis five patients (15.6%; 95% CI: 3.04-28.21%) achieved a partial response, 11 (34.4%) stable disease, and 16 (50%) progressive disease. The median duration of response was 9 months, the median TTP 7 months, and the overall median survival 6.5 months; the overall 1-year survival probability was 27.6%. Grade 3/4 neutropenia was observed in five (15.6%) patients and in two of them associated with fever. Grade 3 anemia and thrombocytopenia occurred in three (9%) and two (6.5%) patients, respectively. Non-hematologic toxicity was very mild with only one episode of grade 4 diarrhea and mucositis, respectively; two (6%) patients complained for grade 3 asthenia. CONCLUSION: The combination of gemcitabine and docetaxel with prophylactic use of rhG-CSF is a safe and well-tolerated regimen for the treatment of patients with advanced NSCLC, who failed front-line treatment with cisplatin-based regimens.

Adult↗

PubMed2001

A dose escalation study of topotecan in combination with epirubicin in pretreated patients with small-cell lung cancer.

PURPOSE: To define the dose-limiting toxicities (DLTs) and the maximum tolerated doses (MTDs) of topotecan in combination with epirubicin in pretreated patients with small-cell lung cancer (SCLC). PATIENTS AND METHODS: Twenty-seven SCLC patients with performance status (WHO) of 0-2 and adequate renal, hepatic, and bone marrow function who had failed EP-containing front-line chemotherapy entered the study. Patients received escalated doses of topotecan (starting dose 0.5 mg/m(2)) for 5 days and epirubicin (starting dose 40 mg/m(2)) on day 8, every 28 days. RESULTS: All patients were assessable for toxicity and 20 for response. The MTD was topotecan 0.90 mg/m(2) and epirubicin 40 mg/m(2) with neutropenia being the most common dose-limiting event. Seventy-three courses were administered. Grade 3-4 neutropenia occurred in 22 (30%) courses, grade 3-4 anemia in 7 (10%), and grade 3-4 thrombocytopenia in 11 (15%). Seven courses were complicated with fever and one patient died of neutropenic sepsis. Grade 3-4 non-hematologic toxicity was mild and infrequent with only grade 2-3 asthenia occurring in 16 (22%) courses. Among 20 patients who were evaluable for response, 16 (80%) were refractory to prior treatment. One patient with refractory disease (5%) achieved a complete response of 14 weeks duration and four experienced stabilization of the disease. CONCLUSIONS: The combination of topotecan 0.90 mg/m(2) on days 1-5, with epirubicin 40 mg/m(2) on day 8, administered every 28 days is a feasible outpatient regimen which merits further evaluation in patients with chemosensitive disease.

Adult↗

PubMed2002

Single-agent pegylated liposomal doxorubicin (Caelix) in chemotherapy pretreated non-small cell lung cancer patients: a pilot trial.

Polyethylene glycol-coated (pegylated) liposomal doxorubicin (PLD) is a new formulation of doxorubicin with peculiar pharmacokinetic and pharmacodinamic properties, a favorable toxic profile and a demonstrated activity in solid tumors. We tested PLD in locally advanced or metastatic NSCLC patients, progressed after a platinum-based first-line chemotherapy. PLD was administered at the dose of 35 mg/m(2) every 21 days. After the first six patients had been accrued, due to the low toxicity shown in the first six patients, the dose was escalated to 45 mg/m(2). Seventeen patients were enrolled in the study and were considered eligible for evaluation of toxicity and response. Stomatitis, palmar-plantar erythrodysaesthesia (PPE) and asthenia were the most common toxicities and affected approximately half of the treated patients. Stomatitis occurred in 8/17 patients and was grade 3-4 in three. PPE was seen in 9/17 and was grade 3 in one. In the group treated at the dose of 45 mg/m(2) PPE was more frequent and severe and required treatment delay in some cases. Other toxicities were equally distributed among the two groups. Hematological toxicity was not common and never reached grade 3-4. However, one patient with grade 2 leucopenia had pneumonia and died. Clinically evident heart failure was never recorded. Left ventricular ejection fraction was assessed in three patients after PLD treatment (in one case after the first course, due to the occurrence of atrial fibrillation, and in two cases after six courses) and was unchanged compared to pre-treatment assessment. One confirmed partial response was observed (5.8%); five patients (29.4%) had stable disease (including one minor response) and nine (52.9%) had disease progression. Median time to progression was 9.5 weeks, median survival 18.6 weeks. PLD at the doses employed in this study can be safely administered and has shown activity in platinum pretreated NSCLC patients.

Adult↗

PubMed2001

Second-line treatment with vinorelbine and carboplatin in patients with advanced non-small cell lung cancer. A multicenter phase II study.

OBJECTIVE: A phase II study was conducted to evaluate the efficacy and toxicity of vinorelbine-carboplatin (VNB-C) combination as a salvage treatment in patients with advanced non-small cell lung cancer (NSCLC) progressing after or failing previous non-platinum, taxane-based treatment. PATIENTS AND METHODS: Thirty-seven patients with cytologically or histologically confirmed NSCLC were enrolled. VNB 30 mg/m(2) was administered on days 1 and 8 and C 300 mg/m(2) on day 1 every 28 days. G-CSF (5 microg/kg per day s.c.) was used prophylactically on days 10-15 in case of grade 3-4 neutropenia or febrile neutropenia after the first cycle. RESULTS: Twenty-nine patients were evaluable for response and all were evaluable for toxicity. In an intention-to-treat analysis, two (5%) complete and four (11%) partial responses were documented for an overall response rate of 16% (95% CI, 4.49-28.84%). Eleven (30%) patients experienced disease stabilisation and 20 (54%) disease progression. The median duration of response was 7.5 months, the median TTP was 9 months, and the median survival was 8.5 months. Patients with objective remission and stable disease had a statistically significant survival benefit over patients with disease progression. Grade 3 and 4 neutropenia occurred in three (8%) and ten (27%) patients, respectively, and six cases (16%) were complicated with fever. Grade 4 thrombocytopenia was documented in one (3%) patient. Non-hematological toxicity was mild, with grade 2 and 3 asthenia reported in 18 (48%) patients. No treatment-related deaths occurred. CONCLUSION: VNB-C combination is well tolerated and retains a notable degree of activity in NSCLC patients progressing after previous non-platinum, taxane-based treatment. Moreover, it confers tumour growth control in a significant proportion of patients, and this seems to be associated with a survival benefit for them.

Adult↗

PubMed2001

Weekly docetaxel as II line therapy in non-small cell lung cancer: an interim analysis of a phase II study.

To evaluate the efficacy and toxicity of weekly docetaxel (D) as II line treatment in non-small cell lung cancer (NSCLC), in November 1999, we started a phase II study on advanced (stages IIIB-IV) NSCLC patients pre-treated with at least one platinum-based chemotherapy regimen with or without radiotherapy. The schedule consisted of D 40 mg/m(2), weekly for 6 weeks, followed by a rest period of 2 weeks, for three cycles or until progression. Eligibility criteria were: histopathologic diagnosis of NSCLC; age <or=75 years; evaluable or measurable progressive lesions; PS (ECOG) 0-2; adequate haematology and biochemistry parameters; no serious concurrent diseases; no symptomatic brain lesions; and informed consent. The end points were assessment of overall response rate, toxicity and quality of life (QoL). Patients were re-evaluated at the end of every cycle. An interim analysis of 18 patients (16 M) was performed. Weekly courses were 132; 16 of 18 patients were evaluable for response and 17 of 18 for toxicity. Two of the 16 patients (12.5%) had a partial response (95% CI: 10.5-14.7%). Haematological toxicity was very mild: grade 1-2 neutropenia occurred in four patients, grade 3 neutropenia in two patients; grade 1-2 anaemia in four patients; and grade 1-2 thrombocytopenia in two patients. Non-haematological toxicity was also very mild, with the exclusion of asthenia (grade 1-2 in ten patients and grade 3 in five patients) and alopecia (grade 1-2 in seven patients and grade 3 in eight patients). No cases of grade 4 toxicity were observed. No QoL evaluations were reported in this interim analysis. In conclusion, these preliminary data confirm that weekly D results in tolerable toxicity in pre-treated NSCLC. Myelo-suppression, the dose-limiting toxicity of every 3 week schedules, is not a clinically relevant problem when D is administered weekly. G-CSF was used only sporadically in four patients, and no febrile neutropenia was reported. Patients were pre-treated with dexamethasone and no allergic reactions were seen. Although the therapeutic activity appears to be comparable to that of every 3 week schedules, more data are necessary before definite conclusions can be drawn. Accrual of patients is still ongoing.

Adult↗

PubMed2002

Gemcitabine (GEM) and carboplatin (CBDCA) versus cisplatin (CDDP) and vinblastine (VLB) in advanced non-small-cell lung cancer (NSCLC) stages III and IV: a phase III randomised trial.

PURPOSE: The combination of Gemcitabine (GEM)/carboplatin (CBDCA) has demonstrated activity in the treatment of stage III and IV non-small-cell lung cancer (NSCLC). This phase III randomized trial compared the response rate, survival rate, and toxicity of the combination of GEM plus CBDCA with the combination of VLB plus CDDP. METHODS: Chemonaïve patients with advanced or metastatic NSCLC were enrolled in the study. Pts were randomized by coin method to receive either cisplatin (CDDP) 70 mg/m(2) on day 1 plus vinblastine (VLB) 6 mg/m(2) on days 1 and 8 (arm A) or gemcitabine 1000 mg/m(2) on days 1 and 8 plus carboplatin 300 mg/m(2) on day 1 (arm B). Both regimens were administered on a 21-day course. RESULTS: A total of 198 patients (99 pts each in arms A and B) were enrolled in the study between July 1997 and April 2000. All pts had an ECOG performance status < or=2. Patients had a median age of 58 years (range, 49-67) in arm A and 59 years (range, 49-69) in arm B. In arm A, there were 15 partial responders (PR), for an overall response rate (ORR) of 15%, compared with three complete responders (CR) and 24 PR, for an ORR of 27% (P<0.05), in arm B. Mean survival times were 7.9 months (95% CI, 7.1-8.0) in arm A and 11.6 months (95% CI, 10.0-13.0) in arm B. One-year survival rates for arms A and B, respectively, were 13 and 36%. Numbers of pts with WHO grad 3/4 hematologic and non-hematologic toxicity in arms A/B were leukopenia 0/2, thrombocytopenia 0/2, alopecia 46/33, neurotoxicity 2/1, and asthenia 35/42. CONCLUSION: The GEM/CBDCA combination showed a higher therapeutic response, an improved 1-year survival, and a similar toxicity profile compared with the VLB/CDDP combination.

Aged↗

PubMed2002

Phase I study of weekly CPT-11 (irinotecan)/docetaxel in patients with advanced solid tumors.

Based on the synergistic cytotoxicity demonstrated in vitro by topoisomerase I inhibitors followed by docetaxel and the feasibility of giving both drugs on a weekly schedule avoiding overlapping toxicities, we designed a phase I trial of weekly CPT-11 (irinotecan)/docetaxel to determine the dose-limiting toxicities (DLT) and the maximum-tolerated dose (MTD) of this combination. Eighteen patients with advanced solid tumors treated with at least one prior chemotherapy regimen were included in this trial. CPT-11 was administered as a 90-min (intravenous) IV infusion followed immediately by docetaxel as a 30-min IV infusion. Both drugs were given on days 1, 8 and 15 in 4-week cycles. Four escalating dose levels of CPT-11/docetaxel (level I: 60/20 mg/m(2), level II: 60/25 mg/m(2), level III: 70/25 mg/m(2), and level IV: 70/30 mg/m(2)) were studied. Forty-seven cycles were administered (range, 1-5 courses) with a median number of 2.6 cycles per patient. Grade 4 leukopenia was the DLT reached at dose-level IV (CPT-11/docetaxel 70/30 mg/m(2)). Four patients had grade 3 anemia at dose levels III (two patients) and IV (two patients), while grade 3/4 thrombocytopenia was not seen. Grade 3/4 non-hematologic toxicities included grade 3 diarrhea in two patients (dose levels II and IV), grade 3 asthenia in one patient (dose level II) and grade 3 stomatitis in one patient (dose level I). The recommended dose of this weekly schedule is CPT-11 70 mg/m(2) and docetaxel 25 mg/m(2). DLT of this regimen is leukopenia, although toxicity is manageable at the recommended dose level. The activity of this regimen is being evaluated in a phase II study in previously treated patients with advanced non-small cell lung cancer.

Adult↗

PubMed2002

Gemcitabine and docetaxel every 2 weeks in advanced non-small cell lung cancer: a phase II study of the Gruppo Oncologico Italia Meridionale.

INTRODUCTION: Platinum-based chemotherapy is the gold standard in advanced non-small cell lung cancer (NSCLC), although with relevant toxic effects. Both docetaxel (DCT) and gemcitabine (GEM) have shown activity as single agent in advanced NSCLC with a different toxicity profile and a lack of cross-resistance. MATERIALS AND METHODS: From April 2000 to May 2001, 47 consecutive patients were enrolled in a multicenter phase II trial. Main inclusion criteria included untreated patients with histologically confirmed NSCLC, age</=70 years, stage IIIB/IV, Eastern Cooperative Oncology Group performance status (PS) 0-2, measurable disease, adequate hematologic, cardiac, hepatic and renal functions, and written informed consent. Treatment schedule consisted of DCT at the dosage of 50 mg/m(2) with conventional steroid premedication and GEM at the dosage of 2,000 mg/m(2). Both drugs were administered every 2 weeks without prophylactic use of growth factors. RESULTS: Enrolled patients included 40 males and seven females with a median age of 65 years, and a median PS 1. There were 26 squamous carcinomas, 13 adenocarcinomas, and eight others, 13 stage IIIB and 34 stage IV. A total of 371 cycles were administered. Overall 18 partial responses were observed (38.3%); 14 patients were considered as stable disease and 13 showed progressive disease. Two treatment-not related deaths occurred before the first disease evaluation was performed. Median duration of response was 6 months (range 2-10) and median duration of survival was 10.5 months (range 1-25+). One year survival probability was 38% (95% CI 25-54%). In a statistical analysis responses were independent to histology or stage. Grade 3-4 toxicity, according NCI criteria, was mild with neutropenia in eight patients (17%), anemia in two patients (4%). Asthenia affected two patients and mucositis occurred in one patient. CONCLUSIONS: In our experience the biweekly combination of DCT and GEM is active and well tolerated and can be administered without G-CSF primary prophylaxis reducing treatment costs. It should be considered as a promising alternative to more toxic platinum-based regimens.

Aged↗

PubMed2003

Gemcitabine and cisplatin versus vinorelbine and cisplatin versus ifosfamide+gemcitabine followed by vinorelbine and cisplatin versus vinorelbine and cisplatin followed by ifosfamide and gemcitabine in stage IIIB-IV non small cell lung carcinoma: a prospective randomized phase III trial of the Gruppo Oncologico Italia Meridionale.

PURPOSE: we carried out a phase III randomized trial to compare vinorelbine-cisplatin regimen to gemcitabine-cisplatin regimen, and to a sequential administration of gemcitabine-ifosfamide followed by vinorelbine-cisplatin or the opposite sequence of vinorelbine-cisplatin followed by ifosfamide-gemcitabine according to the 'worst drug rule' hypothesis in patients with locally advanced unresectable stage IIIB or metastatic stage IV non-small cell lung cancer. The primary endpoint was survival parameters, while secondary endpoints included analysis of response rates and toxicity. PATIENTS AND METHODS: patients were randomized to receive: (a) gemcitabine 1000 mg/m(2) on days 1, 8 and 15 plus ifosfamide 1500 mg/m(2) on days 8-12 with mesna uroprotection (GI regimen) followed by vinorelbine 25 mg/m(2) on days 1 and 8 plus cisplatin 100 mg/m(2) on day 1 (GI --> VC regimen); (b) the opposite sequence (VC --> GI); (c) vinorelbine plus cisplatin as above described (VC regimen); or (d) gemcitabine 1400 mg/m(2) on days 1 and 8 plus cisplatin 100 mg/m(2) on day 8 (GC regimen). All regimens were given every 4 weeks. All patients were chemotherapy naive and had a ECOG PS 0-2. RESULTS: 400 patients were enrolled into the trial. Interim analysis after inclusion of 243 patients showed that ORR were 19% in the GI --> VC arm, 32% in the inverse sequence arm (CV --> GI), 42% in the VC arm, and 30% in the GC arm. The VC arm was statistically superior over the GI --> VC arm (p = 0.0074), but not over the other regimens. Median TTP was 3.1 months in the GI --> VC arm versus 5.0 months in the VC --> GI arm (p = 0.014). For these reasons the GI --> VC and VC --> GI arm were closed since the 'worst drug rule' hypothesis was rejected. Accrual in the VC and GC arms continued up to 140 and 138 patients respectively. Final ORR were 44% for the VC regimen (4 CR), and 34% for the GC regimen (1 CR). This difference was statistically significant (p = 0.032). OS was 9.0 and 8.2 months, respectively, with no statistically significant difference. The 1-year survival rate was 24 and 20%, respectively for VC and GC regimens. As expected the incidence of phlebitis was higher in the VC arm, while thrombocytopenia, flu-like syndrome and asthenia were more frequent in the GC arm. CONCLUSIONS: the results of this trial indicate that the combination of vinorelbine and cisplatin and that of gemcitabine and cisplatin are equivalent in terms of median TTP and OS, although the vinorelbine-cisplatin regimen is associated with a higher ORR. Both regimens may be considered as reference treatments for future studies. Moreover, our data reject the 'worst drug rule' hypothesis of sequential treatments in NSCCL at least with the combination used in this study.

Adenocarcinoma↗

PubMed2003

A phase II multicenter study of combined topotecan and gemcitabine as first line chemotherapy for advanced non-small cell lung cancer.

UNLABELLED: This trial was designed to determine the 1-year survival rate, efficacy, and safety, produced by topotecan and gemcitabine as first line chemotherapy in advanced non-small cell lung cancer (ANSCLC). Fifty-three patients were enrolled; 51 received treatment. Topotecan 1 mg/m(2), days 1-5 and gemcitabine 1 g/m(2) days 1 and 15 were administered IV, each drug over 30 min; cycles consisted of 28 days. Treatment continued until progressive disease or intolerable toxicity. Nineteen patients (36%) had Eastern Cooperative Oncology Group criteria performance status (ECOG PS) = 0, 34 (64%) PS = 1. Median age was 64 years; 37 patients (70%) were male. HISTOLOGY: adenocarcinoma (42%), squamous cell carcinoma (28%), large cell (19%), and unclassified (11%). Among 47 evaluable patients, eight (17%) had partial response, 11 (23%) had stable disease. One-year survival was 39% and median survival was 7.6 months (range, < 1-19.6). Grade 3 and 4 toxicities included neutropenia (53%), anemia (18%), thrombocytopenia (12%), asthenia (8%), and gastrointestinal disorders (8%); three patients (6%) experienced neutropenic fever. There were no treatment-related deaths. The combination topotecan/gemcitabine produced a 1-year survival similar to previous platinum-based regimens, when used as first line chemotherapy for ANSCLC. The toxicity profile was acceptable.

Adenocarcinoma↗

PubMed2003

Phase II study of docetaxel plus enoxaparin in chemotherapy-naive patients with metastatic non-small cell lung cancer: preliminary results.

Activation of coagulation appears to play a role in tumor progression. This report describes the preliminary results of a phase II study using docetaxel plus enoxaparin in 15 patients with stage IV non-small cell lung cancer (NSCLC). Time to progression was the primary endpoint. Several surrogate markers of coagulation and angiogenesis were evaluated. Enoxaparin was administered at a daily dose of 1 mg/kg (subcutaneously). The initial dose of docetaxel was 100 mg/m2, given as a 60 min infusion every 21 days with prophylactic dexamethasone. Eight patients achieved an objective response (53%) and four had stable disease, with a median duration of 3.5 months. The median time to progression was 5 months (range, 2 to >15 months). The median survival was 11 months. The most frequent toxicities were neutropenia and asthenia. No significant bleeding or thrombotic events were observed. Eleven patients had elevated D-dimer plasma levels prior to therapy, and seven of these patients with a response or stable disease had a significant decline of the D-dimer during therapy. There were no consistent changes of the plasma levels of the angiogenic factors, except for transforming growth factor-beta-1 (TGF-beta1). The median baseline level of TGF-beta1 prior to therapy was 34,867 pg/ml. Twelve out of 13 patients who achieved a response or stable disease had a significant reduction of the TGF-beta1 levels during therapy. Enoxaparin in combination with chemotherapy was safe and well tolerated in patients with advanced NSCLC. This preliminary data suggests that enoxaparin may prolong the time to progression, and therefore justify the continuation of this trial.

Aged↗

PubMed2003

Gemcitabine and low dose carboplatin in the treatment of elderly patients with advanced non-small cell lung cancer.

BACKGROUND: Fifty percent of lung cancers arise in patients over 65 years old and 30% in those over 70. The aim of this study was to evaluate response, survival and tolerability of the combination carboplatin-gemcitabine in elderly patients with advanced non-small cell lung cancer (NSCLC). METHODS: Between May 1998 and December 2000, 88 patients were included. Median age was 74 (range 65-83). Treatment consisted of gemcitabine 1250 mg/m(2) (1000 mg/m(2) in the first six patients) on days 1 and 8, and carboplatin AUC=4 on day 1, every 21 days. Prognostic factors for survival were analysed. Performance status (PS) and symptoms were evaluated before and after three and six courses. RESULTS: A total of 400 cycles were administered (median of four per patient). WHO grades 3-4 toxicities were: neutropenia in 13% of the cycles, thrombocytopenia and anaemia in 4.5 and 14.7% of patients in any cycle. There was one treatment-related death. According to the intent-to-treat analysis, 33 patients achieved objective response, 33 had stable disease, and 22 had treatment failure (progression in 18 patients). Median and 1 year survival were 9 months and 34%, respectively. Median time to progression was 8 months. Only disease stage and PS showed independent prognostic value. Comorbidity and PS displayed no close correlation. Symptom improvement was seen as follows: pain (61.7%), dyspnea (50%), haemoptysis (80%), anorexia (62.5%) and asthenia (61.5%). CONCLUSIONS: The combination carboplatin-gemcitabine at these doses is feasible in elderly patients with advanced non-small cell lung cancer. Tolerability and toxicity are acceptable. Response rate and survival stand in the range of the most active regimens. Comorbidity and PS showed prognostic independence.

Aged↗