Mitoxantrone, cytosine-arabinoside and 6-thioguanine (MAT) in the treatment of newly diagnosed acute non-lymphoblastic leukemia in adults.

Between January 1986 and September 1989, 28 patients over the age of 14 years were treated with a combination of mitoxantrone, cytosine-arabinoside (Ara-C) and 6-thioguanine (MAT) at the Kuwait Cancer Control Centre (KCCC). All patients were newly diagnosed cases of acute non-lymphoblastic leukemia (ANLL). Fifty-eight courses of treatment were given as induction and consolidation therapy. The main toxicity was bone marrow suppression. Other toxicities were mainly nausea and vomiting, hepatotoxicity, renal dysfunction and alopecia. In most patients these were mild and tolerable. Complete remission (CR) was achieved in 18 out of 28 (64%) patients. In six patients it was achieved after one course, in 11 patients after two courses and in one patient after three courses. The median survival was 16 months and for those who achieved CR it was 33 months. The actuarial 3 year survival following CR was 43% and the relapse-free survival was 24%. There was little difference in the CR rate for patients below 40 years compared with older patients. However, there was a remarkable difference in survival, with none of the older patients surviving more than 2 years and an actuarial 3 year survival for younger patients of 49%. The study confirms the efficacy of the mitoxantrone-containing combination as a first-line therapy for ANLL.

Serum AFP, hCG and CEA in the management of patients with testicular, ovarian and extragonadal germ cell tumors.

Serum levels of AFP, hCG and CEA were initially and serially measured in 59 patients with testicular germ cell tumors, and serially in 37 with ovarian and 3 with extragonadal germ cell tumors. Patients with seminoma/dysgerminoma or mature teratoma had normal serum AFP and sporadically slightly elevated hCG. Some patients with embryonal carcinoma, pure or with admixture of seminoma, had serum AFP elevated to maximum 100 U/ml, yet its use for monitoring therapy was limited. Patients with yolk sac tumors had elevated AFP and sometimes CEA levels, those with choriocarcinoma had elevated hCG, and those with compound tumors had one or more of the markers highly elevated. High AFP and/or hCG levels indicated the presence of the relevant tumor cells both in the primary and in residual tumor and/or metastases, also those missed in histological material, and thus were useful in restaging. Unfortunately, their absence in serum did not exclude the presence of marker-negative subpopulations of tumor cells. Changes in marker values paralleled the effects of treatment: the level increasing from any nadir heralded recurrence in patients in remission; elevated or increasing levels during therapy implied resistance to the therapy; decreasing levels indicated regression even though a return to the normal range did not mean eradication of all tumor cells.

Combinations of antifungal and antineoplastic drugs with interactive effects on inhibition of yeast growth.

Interactive effects among antifungal and antineoplastic drugs contributed to toxicities when combinations of these drugs were used to inhibit the growth of five Candida spp. Drug interactions were measured by growth inhibition in both liquid and solid media, by viable cell counts and by examination using scanning electron microscopy. Large cooperative effects on toxicity were demonstrated between some antineoplastic and antifungal drugs. For example, positive cooperativity was seen between the antineoplastic drug 5-fluorouracil and combinations of the antifungal agents amphotericin B and miconazole nitrate. Smaller, and often negative, interactions occurred between the antineoplastic drug cyclophosphamide and antifungal drugs. The levels of drugs required for inhibition in combination drug treatments were critically dependent upon the ratios as well as the absolute concentrations of the drugs tested. Drug combinations were selected which inhibit yeast growth at concentrations far below the individual MIC of the drugs. These combinations may prove of value in clinical treatments of cancer patients infected by Candida.

Interactive effects of antifungal and antineoplastic agents on yeasts commonly prevalent in cancer patients.

The effects of combinations of antifungal and antineoplastic drugs on inhibition of the growth of yeasts which commonly infect cancer patients have been analyzed. It was shown that (i) inhibitory drug combinations could be selected in which all drugs were at levels far below their individual MICs; (ii) interactive effects among antineoplastic and antifungal drugs may be very large; (iii) optimum combinations of drugs for inhibition of yeast growth depended upon both the relative and absolute concentrations of the drugs in the mixture; (iv) drug combinations which were effective at low levels in inhibiting one test yeast were also generally effective against other species, but the levels of susceptibilities and, to a lesser extent, the best ratios of drugs in the test combinations varied with species; and (v) to quantitatively evaluate drug interactions, it is necessary to carefully define and control all experimental conditions, absolute and relative concentrations of drugs used, and the organisms tested.

Multifactorial analysis of effects of interactions among antifungal and antineoplastic drugs on inhibition of Candida albicans growth.

Interactions among antineoplastic and antifungal drugs affecting the inhibition of Candida albicans growth are complex functions of the nature of the drugs used in combination, their absolute concentrations, and also their relative concentrations. Studies of drug interactions involving the use of test drugs in fixed concentration ratios can lead to inaccurate conclusions about synergism or antagonism among the drugs. A multifactorial experimental design procedure in which the concentrations of all drugs in test combinations were simultaneously varied has been used to identify and quantify drug interactions. The methods have been applied to combinations of two, three, and four drugs, including antineoplastic drugs, antifungal drugs, and combinations of antineoplastic and antifungal drugs. Results were obtained which allow predictions of effects of combinations and provide maximum effectiveness in growth inhibition with minimum levels of the test drugs.

Effect of antineoplastic agents and X-irradiation on the adherence of Candida spp. to human buccal epithelial cells in vitro.

The role of chemotherapy, X-irradiation and a combination of both on the phenomenon of adherence of yeast to buccal epithelial cells (BEC) was investigated in vitro. Growth of three Candida spp. in the presence of eight of eleven antineoplastic agents led to reduction of adherence of the isolates tested (reduction between 30% and 61% of the control value), and this effect was observed whether exponential or stationary phase Candida cells were used. Exposure of C. albicans to various doses of radiation also led to a reduction in adherence of this yeast to BEC between 31% and 53% of the control value. This reduction was shown to be dose related. Similar results were obtained when BEC were exposed to radiation, and the effects of radiation treatment was accentuated when both yeast and BEC were irradiated simultaneously. Furthermore, treating C. albicans with a combination of chemotherapy and radiation led to the greatest reduction in adherence of yeast to BEC compared to when the yeast was treated with either chemotherapy or radiation alone (reduction between 63% to 74% as compared with control). The possible mechanism/s involved in reduction of adherence of yeast to BEC are discussed.

Hodgkin's disease in children in Kuwait.

Between 1968 and 1981, 78 children younger than age 15 years were diagnosed, staged, treated, and followed up for a minimum period of 2 years. Most cases (64%) were in their first decade and the male-to-female ratio was 1.9:1. Mixed cellularity type occurred in 49% and nodular sclerosis in 32%. Lymphocytic depletion type was rare and occurred in only 4% of the cases. More than one half (53%) had Stages III and IV at presentation. The mediastinum was involved in 38%. The treatment of Stages I and II was mainly by radiotherapy, and Stages III and IV by combination of radiotherapy and chemotherapy. The total survival was 75% and relapse-free survival was 53%. Since 1975, lymphography became a routine investigation and staging laparotomy was performed in selected case. The mantle field was extended to include the para-aortic bar and spleen in Stage II with enlarged mediastinum, Stage IIIs after laparotomy, and cases in which laparotomy was thought to be indicated but was not performed. The new policy resulted in marked improvement in survival (from 56% to 87%) and relapse-free survival (from 32% to 70%). The stage at presentation was the main prognostic factor, although in the second period of the study, the difference between Stage I and II disappeared.