European Journal of Cancer and Clinical Oncology最新文献

To confirm the phenotypic characteristics of lymphokine-activated suppressor (LAS)effector cells, we isolated CD8⁺CD11b⁻ and CD8⁻CD11b⁻ cells from T-cell growth factor (TCGF)-activated peripheral blood lymphocytes (PBL) in 7 patients with gastric carcinoma (4 non-resectable and 3 resectable carcinoma) and 3 healthy controls. Sorted CD8⁺CD11b⁻ cells from 3 of the patients with non-resectable carcinoma and from 1 of the patients with resectable carcinoma showed LAS cell activity. However, the LAS cell activity could not be observed in CD8⁺CD11b⁻ cells from healthy controls. In addition, a sorted CD8⁻CD11b⁻ subset of cells from both cancer patients and control did not express any suppressive activity. These facts clearly show that the cell populations responsible for suppression of cell-mediated antitumour immunity reside within CD8⁺CD11b⁻ T-cells, at least in patients with advanced carcinoma.

70 patients with advanced transitional cell carcinoma of the bladder received methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC). Complete responses (CR) were obtained in 13 of the 67 (19%) evaluable patients and partial responses (PR) in 25 patients for an objective response rate of 57% (95% CI 45–69%). Of the 54 patients who have had a minimum follow-up of 2 years, 8 patients (15%) are disease-free or have stable residual disease. Median survival of the 70 patients was 13 months. Toxicity was acceptable with no drug-related deaths. Because of myelosuppression, only 15 patients (21%) received treatment without delays in drug administration or modifications from the planned schedule. Our results confirm that this regimen is effective, with some patients being long-term survivors.

We investigated alteration in DNA repair during therapy with an immunomodulator. 14 patients with advanced breast cancer were treated parenterally with Iscador, an extract of Viscum album (mistletoe). As a parameter for measurement of DNA repair the incorporation of (³H) thymidine into DNA of unstimulated lymphocytes after ultra violet light (UV) damage was taken. The DNA repair values in the patients were very low before treatment and on day 1: on average 16% of those in a healthy control population. Values started to increase on day 2 and on days 7–9 were on average 2.7 times higher than before treatment. $\text{12}\text{14}$ patients showed an improvement in repair. The values of spontaneous DNA synthesis were not altered during the treatment. We suggest that the increase of DNA repair could be due to a stimulation of repair enzymes by lymphokines or cytokines secreted by activated leukocytes or an alteration in the susceptibility to exogenic agents resulting in less damage.

DABIS maleate is an alkylating quaternary nitrogen. In a phase I study DABIS maleate was administered as a single intravenous infusion once every 3 weeks. 32 patients with solid tumours were studied, at least 3 per dose level (50–1400 mg/m²). Dose-limiting toxicity was severe paresthaesias in the face, around the mouth and in the tongue. Cerebellar ataxia developed at 750 mg/m² or higher. Haematological toxicity was minimal. Nausea and vomiting were mild to moderate. No other non-haematological side-effects were noted. The recommended dose for phase II studies at once every 3 weeks is 750 mg/m² intravenously as a 15 min infusion.

Thirty-six patients with chronic myeloproliferative disorders (CMPD) with thrombocytosis (essential thrombocythaemia 19 patients, chronic megakaryocytic granulocytic myelosis five, polycythaemia vera six, chronic myelogenous leukaemia six) were treated with interferon alfa-2b to reduce the platelet count. The pre-treatment platelet count was in the range 450–700 × 10⁹/L in eight patients, 700–1000 × 10⁹/L in eight and above 1000 × 10⁹/L in 20. In the induction phase of treatment 22 patients were treated with interferon alfa-2b 3 million units (MU) daily subcutaneously for 2 months or until the platelet count returned to normal, if earlier. Fourteen patients received 5 MU interferon alfa-2b daily in the same way. In the maintenance phase the doses were reduced to 3 MU and 5 MU thrice weekly, respectively. Complete response (CR), defined as a reduction of platelet count to below 450 × 10⁹/L, was achieved in 78% of patients (within 2 months of induction in 64%). The platelet depleting effect was dose dependent: CR in 2 months in 52% on 3 MU interferon alfa-2b versus 75% on 5 MU. Reduction of interferon dose was followed by an increase in platelet count in 39% of patients. The white cell count fell by 50% in Philadelphia-negative CMPD. Side effects were common, though generally mild, but led to withdrawal of treatment in six patients. Three patients suffered cerebrovascular events during treatment and one shortly thereafter.

Recent reports have indicated that alpha interferon can be an effective treatment for patients with chronic myelogenous leukaemia (CML) [1]. In order to evaluate the clinical usefulness of interferon alfa-2b, we treated six patients with chronic phase CML and observed their clinical course.

The patients consisted of four males and two females, aged between 39 and 58 years, who had previously received either treatment with busulfan (four patients) or no therapy (two patients). Interferon alfa-2b was administered intramuscularly at a dose of 3–10 million units (MU)/body, either daily or three times per week, for more than 8 weeks.

All six patients showed a fall in white blood cell count from a mean of 101.8 × 10⁹/L (range 15.6–330) before treatment to a mean of 25.7 × 10⁹/L (range 4.0–117) after treatment with interferon alfa-2b. Haemoglobin remained largely unchanged, and platelet counts fluctuated. Two of the six patients also showed a slight reduction in the percentage of Ph¹-positive clones (to 98% and 96%, respectively).

Complete haematological response was achieved in four patients, partial haematological response in one and no response in one. All six patients are alive at a mean of 69 months (range 38–108 months) from diagnosis and are either in chronic phase (five patients) or post bone marrow transplant (one patient).

Major side effects of alpha interferon included fever, general fatigue, and nausea, but all were tolerable.

In conclusion, alpha interferon was useful for controlling blood cell counts in chronic phase CML patients, with tolerable side effects. Five of six patients achieved long-term haematological remission, and alpha interferon slightly reduced the fraction of Ph¹-positive clones in two patients.

4′-iodo-4′-deoxydoxorubicin was administered intravenously to 35 patients with advanced malignant neoplasms. The doses were escalated as follows: 2, 4, 6, 7, 10, 14, 19, 26, 52, 70, 80 and 90 mg/m². Myocardial function was assessed by Holter monitoring and echocardiography. The prevalence of arrhythmias that could be attributed to the drug in the 24 h following infusion was 14.3% (supraventricular) and 10.6% (ventricular). Echocardiographic heart function variables were unchanged at 24 h and 21 days from drug injection. The data indicate the absence of significant, acute cardiotoxic effects of 4′-iodo-4′-deoxydoxorubicin.

Treatment of patients with idiopathic thrombocytopenic purpura (ITP) varies according to the severity of the condition, the patient's age and the phase of the disease. The mainstay of treatment is corticosteroid therapy, with splenectomy for non-responding patients. For the 5%–10% of patients with refractory disease and bleeding problems, intravenous immunoglobulins are often used. Danazol achieves a response in about 30%–40% of refractory patients. At our centre, we have now treated 13 patients with interferon alfa-2b, all of whom had severe steroid-unresponsive ITP of various durations. All patients received 12 injections of 3 million units (MU) interferon subcutaneously three times a week. The platelet count rose significantly in 10 patients after interferon therapy and in one patient during therapy. Three patients had a complete response and eight a partial response. One complete responder relapsed at 5 months but again responded to retreatment with interferon. Responses were similar in splenectomized and non-splenectomized patients, and platelet-associated immunoglobulin levels remained essentially unchanged. Based on a compilation of data from this and other studies, the positive response rate (platelets at least 30–200 × 10⁹/L for at least 6 weeks) is 69% ($\text{22}\text{32}$ patients). The future role and dosage of interferon in ITP remains to be determined and particularly in direct comparison with intravenous IgG therapy.

One hundred and twenty four patients with follicular lymphoma (32 with Stage III and 92 with Stage IV disease) have been randomized to receive chlorambucil alone or chlorambucil plus interferon alfa-2b. Responding patients are then randomized to receive either interferon alfa-2b maintenance therapy for up to 12 months or no further treatment. One hundred and eight patients are evaluable for response, the remainder are still receiving initial therapy. Clinical remission (complete or good partial remission) was achieved in $\text{42}\text{59}$ (71%) patients receiving chlorambucil alone and in $\text{27}\text{49}$ (55%) patients receiving the combination (P = NS). Preliminary analysis of remission duration shows a trend in favour of those patients receiving interferon throughout (P = 0.02). There is no significant difference between the groups in terms of survival, at a median follow up of 2.5 years. Interferon-associated toxicity was minor in most patients but led to discontinuation of therapy in six cases. Larger trials with longer follow-up periods are needed to confirm the beneficial role of interferon in the treatment of follicular lymphoma.