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Palliative care is an important issue to both patients and their families. It is a major contributor to the improvement of the quality of life of patients suffering from chronic diseases as well as terminally ill patients. Its importance increases with the aging of our population. Palliative care has met an enormous success in Western countries and particularly in the U.S.A. over the past two decades. In Lebanon we are far behind the international health community in this field. The educational efforts initiated by medical schools are to be applauded but unfortunately very few institutions offer palliative care to their patients in our country. This is mainly due to the lack of support for such an activity from official health organizations and the lack of information among the public concerning the advantages of palliative care. The efforts of medical schools to incorporate palliative care in their teaching programs will be useless if they are not conjugated with an integration of palliative care in every day's clinical practice.

For chemosensitivity testing, a rapid in vitro colorimetric method (MTT assay) was used. Eleven head and neck cancer cell lines were investigated to distinguish five known active agents from five compounds inactive in phase II studies. Evaluation of the reliability of the assay for assessing drug sensitivity in this tumor cell population was done by correlating the in vitro results with reported in vivo response data. Methotrexate and cisplatin (clinically active) and vindesine and doxorubicin (less active clinically) were recognized in vitro as active and correlated well with clinical experience. Bleomycin (clinically active) was ineffective against some cell lines. The in vitro findings for the clinically inactive drugs (deoxyazacytidine, lomustine, and carmustine) also corresponded. Amsacrine and etoposide, contrary to clinical experience, showed activity in vitro. Further comparison of MTT assay results with clinical data is warranted and essential before its use in large-scale drug screening studies.

In an ongoing phase II trial conducted in advanced breast cancer, we tested a therapy schedule consisting of continuous, 24-h infusion of 5 g/m2 ifosfamide (IFO) in 3 1 dextrose saline with mesna (MSN), repeated every 3 weeks until disease progression. Since September 1988, 16 heavily pretreated patients with advanced disease (11 with visceral lesions) considered refractory to standard chemotherapy (regimens always including cyclophosphamide) have been included. Objective partial remissions were observed in two cases (one in liver and one in soft-tissue and pleural lesions), and disease stabilization for at least 3 months occurred in four cases. No treatment-related death was recorded and tolerance was judged to be excellent (six cases) or acceptable in all instances. The haematological toxicity consisted mainly of transient leucopenia (nadirs evaluated by WHO scale as grade 3 in 43% and grade 4 in 29%), sometimes associated with thrombocytopenia (grade 3 in 7% and grade 4 in 7%). Other side effects included nausea and/or vomiting (grade 3-4 in 33%); worsening of preexisting alopecia (five cases); haemorrhagic cystitis (one case); mild, transient somnolence (two cases); and moderate fluid retention (two cases). We concluded that infusion of 5 g/m2 IFO over 24 h with MSN rescue might represent an acceptable second- or third-line salvage regimen. Close monitoring of haematological and renal function parameters is recommended. A larger number of patients will be treated in a continuation of this study to evaluate the true response rate within narrower confidence limits.

Trilostane (4- α -5-epoxy-17 β - hydroxy -3-oxo-5- α -androstan-2-carbonitrile) is a modified steroidal molecule. In vitro and in vivo studies in rats have shown that it inhibits adrenal, ovarian and placental steroid synthesis. It seems to act by exerting a selective blockade on 3 β -hydroxysteroid dehydrogenase. In this study, we investigated whether this molecule interacts with hormone receptors for estrogen, androgen or progesterone. We also tried to demonstrate the effect which Trilostane may have on cellular cultures of human mammary carcinoma (MCF-7 Evsa-T). We also studied hormonal modifications in a series of 12 patients treated with different doses of Trilostane, since this drug is supposed to inhibit the production by the adrenal glands of mineralocorticoids, of glucocorticoids and of the precursors of estrogens. Our results indicate that Trilostane does not react with any of the main hormonal sex steroid receptors, nor does it interfere with cultures of human mammary cancer cells either containing estrogen receptors and therefore allegedly hormone-dependent (MCF-7 line), or estrogen receptor-negative cells, presumably independent of hormonal manipulations (Evsa-T cell line). Finally, endocrine studies on postmenopausal women with advanced breast cancer show that Trilostane significantly reduces the plasma levels of estrone and of its major androgen precursor (androstenedione). However, the latter inhibition is no different from that exerted by hydrocortisone acetate administered alone at a dose of 40 mg/day . The results of clinical trials comparing hydrocortisone alone with hyrocortisone plus Trilostane are awaited.

We conducted a phase I trial with the combination carboplatin (CBDCA)-etoposide (VP- 16 ) in thoracic cancer. CBDCA, at a starting dose of 300 mg/m 2 d 1 , was associated with a fixed dose of VP- 16 ( 100 mg/m 2 d 1–3 ). Escalation of doses was permitted after three patients entered at each dose level without grade IV toxicity. As expected, hematologic toxicity was the limiting factor. Severe myelosuppression (grade IV) occurred in three out of four patients treated at 350 mg/m 2 . Only three out of 19 patients treated at 325 mg/m 2 exhibited a reversible grade IV hematologic toxicity. Other toxicities were mild and acceptable. Among 15 evaluable patients three showed a partial response. Two of the three responders have previously had a progression while receiving cisplatin and etoposide. The recommended dose of carboplatin to be associated with VP- 16 ( 100 mg/m 2 d 1–3 ) is thus 325 mg/m 2 d 1 .

ACTIVE chemotherapeutic agents are rare, provide only palliation in most advanced solid tumors and are responsible for a limiting dose-dependent toxicity in normal cells. Therefore it is important to develop new active and less toxic drugs for the treatment of cancer. The classical murine based screening program for new drugs, used by the NC1 over the last three decades, has been rather disappointing and effort has been put into developing analogs to known active drugs with the hope of finding either a wider and different range of activity or a lower toxicologic profile with respect to the parent compounds. Improving the results achieved with available active drugs can be performed by combination therapies, or by associations with potentiating agents or with other therapeutic modalities such as irradiation, immunotherapy or hyperthermia. The prediction of individual response to chemotherapy is a perpetual challenge in cancer. Clonogenie and non-clonogenic in vitro chemosensitivity assays using fresh tumor biopsies from investigated patients have been very accurate in such predictions, particularly when the tumors were resistant to drugs [ 11. However, the routine use ofsuch assays has historically been limited by the poor growth of these fresh tumors yielding only few successful and interpretable results. Fortunately, improved culture methods developed over the last few years seem to have overcome this problem [24]. Starting from the observation that drugs inactive in the murine screening model were cytotoxic in vitro against fresh tumors [5], the NC1 is currently investigating a new in vitro screening program described

Eighteen adult patients with solid tumors were treated with oral menogaril, a new anthracycline antibiotic active against human breast cancer after intravenous administration. The drug was given orally on 3 consecutive days every 4 weeks at doses ranging from 50 to 175 mg/m2/day. Reversible and dose-related leukopenia was the dose-limiting toxicity. Thrombocytopenia was less frequent. Hematologic toxicity was maximal usually 2 weeks after treatment and recovery usually occurred within 4 weeks. At doses from 50 to 150 mg/m2/day, non-hematologic side-effects of oral menogaril were infrequent and mild and consisted of nausea and vomiting (one patient), alopecia (two patients), mucositis (two patients) and liver function test abnormalities (three patients). The single patient treated at a daily dose of 175 mg/m2/day developed grade IV leucothrombocytopenia, with fever and gastrointestinal bleeding. This was followed by heart failure and the patient died from multisystem organ failure. Peak plasma concentrations of menogaril ranged from 0.043 to 0.409 microM and were linearly correlated with the dose. Similarly, the area under the plasma concentration versus time curve varied from 0.33 to 9.59 microM X h and was linearly correlated with the dose. The mean harmonic half-life was 11.3 +/- 6.4 h. A comparison of the data from the present trial and our previous study with intravenous menogaril indicates a bioavailability of 32 +/- 12%. There was an excellent relationship between the white blood cell decrease (as a percentage of the pretreatment value) and several pharmacokinetic parameters; the best correlation was obtained with the plasma concentration of menogaril at 4 h after treatment. A dose of 150 mg/m2/day for 3 consecutive days is recommended for phase II trials with oral menogaril but the bioavailability of the drug should be monitored carefully and, more specifically, the concept of a pharmacokinetic adjustment of the dose of menogaril should be evaluated prospectively.