Cisplatin, gemcitabine and vinorelbine in locally advanced or metastatic non-small-cell lung cancer: a phase I study.

Purpose: The objective of this study was to determine the maximally tolerable doses (MTDs) of vinorelbine (VNR) and gemcitabine (GEM) when combined with a fixed dose of cisplatin (CDDP).

Patients And Methods: Chemotherapy-naive patients with stage IIIB-IV non-small-cell lung cancer (NSCLC) received a fixed dose of CDDP (50 mg/m2) and escalating doses of VNR (starting from 20 mg/m2) and GEM (starting from 800 mg/m2) on days 1 and 8, every three weeks. The single escalation of GEM alone, by 200 mg/m2 at each step, was initially planned up to a dose of 1,200 mg/m2, to be followed by increments of the VNR dose of 5 mg/m2 at each step.

A phase I study of cisplatin, methotrexate, levofolinic acid and 5-fluorouracil in advanced squamous cell carcinoma of the head and neck.

Twenty-one chemotherapy-naive patients with unresectable or metastatic squamous cell carcinoma of the head and neck (SCCHN) received a combination chemotherapy including cisplatin (CDDP), methotrexate (MTX), folinic acid (LFA) and 5-fluorouracil (5-FU). The doses of the 3 cytotoxic drugs were escalated until dose-limiting toxicity occurred in more than 1/3 of the patients. The treatment was generally well tolerated; no toxic deaths occurred.

Weekly paclitaxel/cisplatin with concurrent radiotherapy in patients with locally advanced non-small cell lung cancer: a phase I study.

We designed a phase I study to determine the maximum tolerated doses of weekly cisplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (doses escalated alternately) when given concurrently with standard or hyperfractionated radiotherapy (RT) and to define the nature of the dose-limiting toxicity. Chemotherapy-naive patients with locally advanced non-small cell lung cancer received weekly combination cisplatin/paclitaxel with concurrent local RT. Radiation therapy was initially given at the dose of 1.

Fotemustine and dacarbazine plus recombinant interferon alpha 2a in thetreatment of advanced melanoma.

Forty-three consecutive patients with advanced melanoma not previously treated with cytotoxic drugs (22 of them had already received adjuvant recombinant interferon alpha 2a (rIFN alpha 2a)) were given a combination of intravenous (i.v.) fotemustine (FM), 100 mg/m2 on day 1, and dacarbazine (DTIC), 250 mg/m2 i.

Weekly paclitaxel and cisplatin with concurrent radiotherapy in locally advanced non-small-cell lung cancer: a phase I study.

Purpose: Both cisplatin (CDDP) and paclitaxel have shown good antitumor activity in non-small-cell lung cancer (NSCLC) patients and are able to potentiate the antitumor effects of radiation therapy (RT). This study aimed to determine the maximum-tolerated doses (MTDs) of CDDP and paclitaxel (escalated alternately) when given concurrently with RT and to define the nature of the dose-limiting toxicity (DLT).

Patients And Methods: Chemotherapy-naive patients with locally advanced NSCLC received six weekly administrations of a CDDP-paclitaxel combination with concurrent local RT.

Tc-99m MIBI scintigraphy in patients with lung cancer. Comparison with CT and fluorine-18 FDG PET imaging.

Tc-99m MIBI imaging has been used to evaluate patients with different neoplastic disorders, but its role in nuclear oncology has not been definitely established. In this study, we compared the results of Tc-99m MIBI (planar and SPECT imaging) with those of F-18 FDG PET radionuclide studies in 19 patients who had proven lung cancer. One patient was studied in follow-up.

Cisplatin-paclitaxel weekly schedule in advanced solid tumors: a phase I study.

Purpose: The objective of our study was to determine the maximum tolerable doses (MTDs) of both paclitaxel and cisplatin when given in a weekly schedule alone or simultaneously with G-CSF in advanced solid neoplasms.

Patients And Methods: Patients with advanced cancer either chemotherapy-naive or resistant to standard treatments received paclitaxel in a three-hour infusion followed by cisplatin, with or without the addition of r-HuG-CSF (5 micrograms/kg s.c.

Phase I study of vinorelbine and paclitaxel in small-cell lung cancer.

Background: Vinorelbine and paclitaxel interfere with mitotic spindle function through different mechanisms of action. Both of the drugs show antitumor activity in small-cell lung cancer when used as single agents; furthermore, in vitro and in vivo studies have shown a synergistic activity between the two drugs.

Patients And Methods: Patients with small-cell lung cancer no longer amenable to conventional treatment were entered into a phase I study in which vinorelbine was given at a fixed dose of 30 mg/m2 by 15-min intravenous infusion, whereas paclitaxel was given by 3-h infusion starting 1 h after vinorelbine at an initial dose of 90 mg/m2, which was subsequently escalated by 30-mg/m2 steps.

Significance of methotrexate serum level achieved in patients with gastrointestinal malignancies treated with sequential methotrexate, L-folinic acid and 5-fluorouracil.

Twenty-one patients affected by advanced carcinoma of the digestive tract, all but 2 previously treated, received on day 1 every 2 weeks a 2-hour intravenous (i.v.) infusion of methotrexate (MTX), 250 mg/m2, followed 24 h later by a 2-hour i.

Thymostimulin treatment of hepatocellular carcinoma on liver cirrhosis.

Hepatocellular carcinoma (HCC) on liver cirrhosis (LC) is a neoplasm with a poor prognosis. Only 10-36% of patients have resectable tumors at presentation, systemic chemotherapy is seldom useful and loco-regional treatments are feasible only in selected cases. On the basis of the possible role of depression of immune function in the pathogenesis of HCC on LC, we employed thymostimulin in the treatment of patients with unresectable HCC on LC, with the aim of influencing the course of the disease.

Nerve growth factor reduces apoptosis of axotomized retinal ganglion cells in the neonatal rat.

It has recently been reported that the degeneration of retinal ganglion cells induced by transection of the optic nerve in the neonatal rat is due to an active process of apoptosis, as opposed to passive necrosis. Here we tested whether the administration of the trophic factor nerve growth factor could prevent the apoptotic death of the axotomized cells. We administered nerve growth factor by two intraocular injections, one immediately after the lesion and the second 12 h later.

Expression of insulin-like growth factor (IGF)-II and IGF-I receptor during proliferation and differentiation of CaCo-2 human colon carcinoma cells.

We have studied the expression of insulin-like growth factor type II (IGF-II) and its autocrine role during the proliferation and differentiation of the CaCo-2 colon carcinoma cell line. IGF-II RNA levels were high in proliferating cells and decreased by more than 10-fold when cells ceased to proliferate and differentiated. Immunoreactive IGF-II protein was high in the conditioned media of proliferating cells and decreased 20-fold in the media of differentiated cells.

Mitomycin C and mitoxantrone in anthracycline-pretreated advanced breast cancer patients. A phase II study.

Twenty-one patients with anthracycline-pretreated advanced breast cancer were treated with mitomycin C plus mitoxantrone (MM), 10 mg/m2, on day 1 of a 28-day cycle. All patients were evaluated for toxicity and response. Overall, 83 cycles were administered, with a median number of 4 cycles per patient.

Afferent spontaneous electrical activity promotes the survival of target cells in the developing retinotectal system of the rat.

This study was undertaken to investigate the role of afferent spontaneous electrical activity in regulating death of target cells in the developing mammalian visual system. We show here that naturally occurring cell death in the rat superior colliculus is greatly augmented when the spontaneous firing of retinal ganglion cells is transiently blocked with TTX. An increased number of dying cells is already observed after 1 hr of afferent blockade.

Different effects of intracranial and intraorbital section of the optic nerve on the functional responses of rat retinal ganglion cells.

A lesion to the optic nerve of adult mammals leads to the retrograde degeneration and finally to the death of injured retinal ganglion cells. In this study, we have evaluated the effects induced by different sites of axotomy on the functional changes occurring in the retinal ganglion cells after optic nerve section. We have investigated the functional properties of retinal ganglion cells of adult rats by recording the retinal responses to patterned stimuli (pattern electroretinogram) after unilateral section of the optic nerve at two different levels: intraorbital and intracranial.

Transplant of embryonal nervous tissue preserves the responses of rat retinal ganglion cells after section of the optic nerve.

We have investigated the effectiveness of embryonal tectal tissue transplants in preserving the physiological activity of lesioned ganglion cells by recording the visual responses from the adult rat retina after section of the optic nerve, with or without transplants of embryonal nervous tissue on the stump. We have found that transplant of embryonal nervous tissue at the level of the optic nerve section has dramatic effects in preserving visual retinal responses to patterned stimuli for times as long as five months after surgery. By this time retinal responses to patterned stimuli have almost completely disappeared in control animals with optic nerve section alone.

Pattern ERG in rats following section of the optic nerve.

The aim of this study is to investigate in the rat the properties of the pattern electroretinogram (ERG) and to assess whether it depends upon the functional integrity of ganglion cells. Flash and pattern ERG were recorded from urethane anaesthetized hooded rats. The pattern ERG was evoked by phase alternating gratings of various spatial frequencies and contrasts.

Topically applied levobunolol does not cause changes in the corneal endothelium.

The corneal endothelium was examined in ten patients suffering from ocular hypertension before, during and after four months of topical levobunolol treatment. The untreated fellow eye served as a control. The number of endothelial cells, determined with a McIntyre eyepiece and an Eisner's contact lens, was not affected by levobunolol therapy.

Functional dissociation of the hemispheres in the discrimination of complex gratings near the vertical meridian.

It was previously shown that the discrimination of complex gratings differing in the spatial phase of their harmonic components is performed more accurately when the stimuli are presented in the left than in the right visual hemifield, provided that the stimuli are separated at least 2 deg from the vertical meridian (VM) and/or their spatial frequency exceeds 2 c/deg. Here we report measurements of reaction times (RT) for the discrimination of complex gratings presented laterally at various distances from the VM. The (choice) RTs are found to be longer in the right than in the left hemifield even for stimuli of low spatial frequency at 1 deg from the VM.

[The pathogenesis of inadequate cerebral circulation in the aged].

A physiopathologically oriented classification is proposed for cerebral circulatory insufficiency to cover forms caused by intra- and extracranial vascular disease, and those of cardiac and non-cardiac extravascular origin. The aetiopathogenetic aspects of the matter are discussed, and some clinical pictures of particular geriatric interest are described. Lastly, attention is given to the dysmetabolically induced instances of cerebral distress that are often observed in the aged.