Carboplatin and gemcitabine in the palliative treatment of stage IV non-small cell lung cancer: definitive results of a phase II trial

BACKGROUND: Cisplatin-containing regimens represent the gold standard in the treatment of advanced non-small cell lung cancer, but carboplatin is often preferred for its better toxic profile when palliation is the aim of the treatment. The synergistic effect and tolerability of carboplatin-gemcitabine combination are well known. In this phase II trial, we evaluated the activity and safety of a schedule with carboplatin and gemcitabine, defined in our previous phase I trial. METHODS: Thirty-seven patients with measurable stage IV non-small cell lung cancer were treated with carboplatin, AUC 4.5 mg/ml/min on day 1, and gemcitabine, 800 mg/m2 on days 1 and 8, every 21 days. All patients were treated until disease progression or intractable toxicity and were evaluated before each course of chemotherapy for toxicity and after every 3 courses for response. RESULTS: After a median follow-up of over 10 months, complete response, partial response, and stabilization of the disease were observed in 3 (8.1%), 9 (24.3%), and 15 patients (40.5%), respectively. Median time to progression was 7 months. At this writing, 27 patients have died, with a median survival of 10 months, and 29 (78.3%), 16 (43.2%), and 11 (29.7%) patients are alive after 6, 12, and 15 months of follow-up, respectively. Toxicity was mild, and mainly hematological, with a significant correlation with the number of courses of chemotherapy (P = 0.0003). CONCLUSIONS: Our results are comparable with those reported in the literature and confirm the good activity and tolerability of the carboplatin-gemcitabine combination. Up to 4 courses of chemotherapy with carboplatin and gemcitabine may represent an interesting option in the palliative treatment of non-small cell lung cancer.     

Optimization of the schedule of gemcitabine-cisplatin combination as induction regimen for patients with biopsy-proven stage IIIa N2 - stage IIIb non-small-cell lung cancer: a prospective phase-II study

Aim of this study was to define the optimal schedule of gemcitabine (GCB)\cisplatin (CDDP) combination as induction chemotherapy (CHT) in patients with stage IIIa pN2-IIIb non - small-cell lung cancer (NSCLC). Fifty patients with mediastinoscopically-proven stage-IIIa pN2 -IIIb NSCLC were treated with 3 cycles of induction CHT followed by surgery (if staged IIIa) and three-time-daily accelerated radiotherapy. Chemotherapy initially consisted of 3 courses of CDDP 100 mg\m(2) d1 plus GCB 1000 mg\m(2) dd 1,8,15 repeated every 4 weeks, than was modified in CDDP 80 mg\m(2) d1 plus GCB 1250 mg\m(2) dd 1,8 repeated every 3 weeks. Twenty-nine four-week scheduled treatment cycles were firstly administered to 10 patients (pts): treatment-related toxicity, mainly hematological, caused a dose-reduction or treatment omission on day 15 in 65% of cycles. After the protocol was amended, 119 three-week scheduled treatment cycles were administered to 40 pts. Treatment-related toxicity of the new schedule caused a dose-reduction or treatment omission in only 10% of cycles, no patients requiring chemotherapy discontinuation. Thirty-seven out of fifty patients (74%, 95% CI: 60-85%) achieved a partial response, 7 had stable disease and 6 had disease progression. Similar activity was seen with both schedules. One nodal pathological complete remission was observed among the 24 pts who underwent surgery. At present, with a median follow-up of 13 months (mos), 2-year (y) survival of all the 50 pts and of the 24 pts staged IIIa who underwent surgery is estimated as 37% (95% CI: 24-58%) and 47% (95%CI: 27-80%), respectively. When given as induction chemotherapy, a three-week schedule of CDDP plus GCB combination appeared to be effective, with lower toxicity and better compliance than a four-week schedule.     

Ultrasound (US) guided central venous catheterization of internal jugular vein on over 65-year-old patients versus blind technique

BACKGROUND AND OBJECTIVES: Performing a central venous catheterization (CVC) on older patients for long-term central intravenous therapy could be a very important procedure. It could be associated with a high incidence of related complications, especially on over 65-year-old, high risk, selected patients. METHODS: The authors analyzed the results of 72 central venous CVC of internal jugular vein performed on over 65-year-old patients with ultrasound (US) guide from January 1998 to April 2003. RESULTS: The average performing time was 4 min, with 98.7% of success, 0% of major complications, and 4.1% of minor complications (one mild vagal hypotension and two catheter dislocation). CONCLUSIONS: The US guided technique is a safer procedure especially in older patients; it affords an easier and more rapid cannulation of a central vein, drastically reducing major and minor complications.     

Cine-MR in a patient with suspected normal pressure hydrocephalus

The case of a patient with predominant short-term memory and CT pattern suggestive of of normal pressure hydrocephalus, is discussed. Clinical and CT findings did not allow to predict the clinical response to a possible ventriculoperitoneal shunt. On MRI more accurate morphological evaluation with cine-MR functional assessment was obtained. Calculated CSF flow indexes evidenced hyperdynamia usually associated with a good outcome after ventriculoperitoneal shunting.     

Tailoring immunosuppressive therapy in interstitial lung diseases

An increasing number of immunosuppressive drugs have become available for clinical use over the past few years. Respiratory medicine has not been excluded from the growing enthusiasm devoted to the use of novel immunosuppressants. New agents are currently undergoing clinical trials in pulmonary disorders characterized by acute or chronic inflammation, the "optimal" immunosuppressive strategy for the cure of interstitial lung diseases in the next decade being forthcoming. An example of this fervour may be found in this issue of the Journal; data have been provided on the effectiveness in clinical use of an inhibitor of nucleotide synthesis, leflunomide, in chronic sarcoidosis. The great choice of available agents could allow us to select the best therapeutic regimen for an individual patient, however, this requires a comprehensive knowledge of the modes of action of the immunosuppressants we are planning to use. The present review provides an update of current understanding on the molecular mechanisms of some important immunosuppressants that are expected to play a role in the therapy of interstitial lung diseases.     

Fatty acid synthase is required for the proliferation of human oral squamous carcinoma cells

Fatty acid synthase (FAS) is the enzyme responsible for the endogenous synthesis of saturated long-chain fatty acids from the precursors acetyl-CoA and malonyl-CoA. A growing body of evidence indicates that FAS is over expressed in several human cancers, such as prostate, breast, bladder, liver, lung, melanoma and oral squamous cell carcinoma (SCC). In the present study we used human oral SCC cell lines (SCC-4, -9, -15 and -25) as a model to investigate the role of FAS in the pathogenesis of oral cancer. RT-PCR and western blot experiments demonstrated that FAS is differentially expressed by the four oral SCC cell lines, with the highest production in SCC-9 followed by SCC-25. FAS expression in SCC-4 and -15 was similarly lower than the other cell lines. Proliferation curves and immunocytochemistry for PCNA and Ki-67 demonstrated that SCC-25 has the highest proliferative potential. In addition, the specific inhibitor of FAS activity cerulenin was able to significantly reduce the proliferation of oral SCC cells. Expression of androgen receptor was low in SCC-4, -9 and -15 and undetectable in SCC-25, whereas EGFR and c-erb-B2 were expressed in high amounts by the four cell lines. Immunocytochemical reactions showed that SCC-25 expresses higher levels of EGF compared to the other three cell lines. Finally, oral SCC cells exposed to nanomolar concentrations of exogenous EGF presented a reduction in the FAS protein levels concomitant with a decrease in their proliferation rates. Taken together, our results indicate that FAS is expressed in an apparently androgen-independent fashion in oral SCC cells and it is necessary for their proliferation.     

Safety and tolerability of oral erectile dysfunction treatments in the elderly

Erectile dysfunction (ED) is a common medical condition that affects the sexual life of millions of men worldwide. It is generally accepted that sexual function tends to decline with aging, which is often associated with a higher prevalence of sexual problems, including ED and loss of libido. As the mean age of men seeking medical help for sexual dysfunction continues to increase, it is important to assess the safety and tolerability of currently available medical treatments in elderly men, who often share other co-morbidities that should be carefully evaluated when any type of ED therapy is considered. With this aim in mind, a MEDLINE search was conducted from 1 January 1998 to 31 May 2004 to identify studies assessing the efficacy, safety and tolerability of treatments for ED in the elderly. Particular care was taken to assess the cardiovascular safety of oral drugs for ED in this subset of patients, who often have multiple cardiovascular risk factors which contribute to a complicated clinical scenario. The most important conclusion of the paper is that the high efficacy, reliability, safety and tolerability of oral ED treatments makes them appropriate first-line therapies for elderly patients with ED.     

Mitochondrial myopathy: two case reports

Mitochondrial myopathy is a genetic disorder characterized by chronic progressive external ophthalmoplegia and upper eyelid, ptosis which occurs before 30 to 40 years of life. The authors reviewed the literature and reported two cases of reading diplopia in female patients.