European Journal of Cancer and Clinical Oncology最新文献

A multicentre clinical trial was carried out in order to evaluate the effect of interferon (IFN) in patients with multiple myeloma. Patients (n = 120) who had shown response to conventional intermittent melphalan-prednisone induction therapy, and achieved a plateau phase, were randomized at that point to receive either interferon alfa-2b in a dose of 5 million units (MU) three times per week or no therapy. This report presents the results of an interim analysis, performed when the patients had been followed for a median of 20 months. The duration of the plateau phase was significantly longer in the IFN arm (59 weeks), compared to the no therapy arm (26 weeks). A total of 34 deaths have occurred, 13 in the IFN arm and 21 in the no therapy arm. In spite of the high median age of the patients studied (70 years), most patients were able to tolerate a full or only slightly reduced IFN dose.

A STUDY was undertaken in which eight patients aged 22 to 80 years with Ph¹-positive chronic myelogenous leukaemia (CML) were treated with interferon alfa-2b at an initial dose of 4 million units (MU)/m² per day.

One patient in accelerated phase was pretreated with vindesine and prednisone, and showed an increase in white blood cell count during interferon treatment. In addition, one of the seven patients in chronic phase, who was previously untreated, dropped out because of skin eruption. According to the response criteria of Alimena et al. [1], three of the other six patients in chronic phase achieved haematological response (two complete, one partial) and two had cytogenetic improvements (one complete, one minor).

Adverse effects included fever (six patients), malaise (two), anorexia (one), delirium (one), liver disorder (two) and skin eruption (one).

We present here the pre-treatment features and clinical course of a patient who achieved complete cytogenetic response (CCR). A 32-year-old female patient, admitted to hospital because of marked hepatosplenomegaly (spleen 11 cm under the navel) and anaemia, was diagnosed as having Ph¹-positive CML and treated with interferon alfa-2b 6 MU/body daily for 4 months and twice weekly thereafter. Her pretreatment blood cell counts were as follows: red blood cells 2.17 × 10⁶/μL; haemoglobin 6.6 g/dL; white blood cells (WBC) 206,700/μL; and platelets 610 × 10³/μL.

The patient achieved complete haematological response [1] at the 32nd week of interferon administration, together with resolution of hepatosplenomegaly.

Cytogenetic and molecular biological analyses revealed partial suppression of the Ph¹ chromosome at the 38th week (75% Ph¹-positive) and complete cytogenetic response (CCR, 0% Ph¹-positive) at the 140th week of interferon treatment.

In conclusion, long-term administration of interferon alfa-2b alone induced complete suppression of the Ph¹ chromosome in one patient with Ph¹-positive CML, and the duration of this CCR is more than 4 months. The combination of alpha interferon with other treatments in order to enhance cytogenetic improvement should be investigated.

We have administered interferon alfa-2b, alone or in combination with chemotherapy, to 126 Ph¹-positive chronic myelogenous leukaemia patients. Of 71 early chronic phase (CP) patients (< 12 months from diagnosis), 41 (58%) obtained a complete haematological response (CHR). Daily interferon was more effective than intermittent administration. In previously untreated patients, the response was significantly influenced by risk status at diagnosis. Thirty-four out of 71 (48%) patients improved cytogenetically, the median of Ph¹+ mitoses declining from 100% to 66% with complete Ph¹-suppression in one case. Of 46 late CP patients (> 12 months from diagnosis), 32 (70%) achieved CHR with interferon alone or combined with chemotherapy. All 10 patients with disease well controlled by chemotherapy obtained stable CHR with interferon alone. Of 36 partial responders to conventional chemotherapy, 22 (61%) obtained CHR on interferon plus low-dose hydroxyurea. Ph¹ mosaicism was reached by 16 (35%) late CP patients (median Ph¹+ cells 75%). Of nine accelerated phase patients on interferon plus chemotherapy, one attained CHR, and two responded partially. At a median follow up of 36 months, of 41 CHR patients in early CP, 15 are controlled on interferon, 12 have had autologous bone marrow transplantation (BMT), and two allogeneic BMT. Blastic transformation (BT) has occurred in eight of 41 CHR patients (19%) versus 17 of 30 (57%) non-responders and partial responders to interferon. At a median follow up of 22 months, of 32 late CP patients obtaining CHR, 26 remain on interferon, one had allogeneic BMT, one had autologous BMT, and one developed BT (versus five out of 14 with less than CHR). These studies confirm the haematological and cytogenetic efficacy of interferon in CML and indicate that the disease status at the start of treatment is critical in determining the success of therapy.

Left handedness was found to be significantly less common among patients with breast cancer in southern Sweden (1.5%) than among a female referent population (5%) (P<0.0025). The findings lend support to theories suggesting that hormonal factors in early life are of importance both for handedness and for the risk of breast cancer.

Using an antiserum to epithelial membrane antigen we have screened multiple bone marrow aspirates from 350 patients with primary breast cancer taken at the time of initial surgery. 89 (25%) patients were found to have micrometastases and their presence was related to pathological size (P < 0.01), the presence of peritumoral vascular invasion (P < 0.001), and positive lymph nodes (P < 0.005) but not menopausal status. At a median follow-up of 76 months (range 34–108) 107 patients had relapsed with distant metastases. 48% (43 of 89) of these patients had micrometastases initially compared with 25% (64 of 261) who did not (P < 0.005). The test predicts for relapse in bone (P < 0.01) and other distant sites excluding bone (P < 0.001) and is associated with a shorter overall survival (P < 0.005). We conclude that the detection of micrometastases signals a high likelihood of early relapse and decreased survival in breast cancer.

From 1963 to 1988, 281 patients with newly diagnosed follicular lymphomas were treated and followed at the Foundation Bergonié. Distribution of stages was: 72 I, 61 II, 83 III and 65 IV. Within stage III, two subgroups were retrospectively defined: stages III₁ (32 cases) included patients with less than 8 involved sites, only 1 or 2 above diaphragm, and no spleen or mediastinal enlargement. Stage III₂ (51 cases) included the remaining stage III cases. Median follow-up was 9 years. Complete remission (CR) rate was 82%. 10-year overall survival (OS) and time to treatment failure (TTF) rates were, respectively 38% and 29.5%. 10-year time to relapse (TTR) rate was 36%. Statistical analyses showed concordant results with two main prognostic factors: age ($\text{<60}\text{>60}$) and stage (I to III₁/III₂ and IV). Age was the most important factor for OS analysis and stage for CR and TTR analysis. This leads to only three prognostic groups with different outcome. The first includes younger patients (<60 years) with limited stages (≤III₁); the second, patients either older than 60 or with advanced stages; the last, elderly patients with advanced stages. CR rates of these three groups were, respectively 97%, 75% and 57%. 10-year OS were, respectively 73.5%, 27% and 0%; 10-year TTR were 54%, 22% and 0%. These results have lead to data which are easy to handle and which can help to establish a rationale for further prospective trials.

46 patients with malignant pleural mesothelioma were entered in a phase II study of mitoxantrone 14 mg/m² every 3 weeks. Histology was confirmed by a pathology panel. None of the patients had received previous chemotherapy. Toxicity was mainly mild gastrointestinal and haematological side-effects. Out of 34 patients evaluated for response, only 1 partial response was recorded. Mitoxantrone at this dose and schedule has marginal activity in malignant mesothelioma.

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.