Giovanna Cavazzini

Low dose arabinosyl cytosine for treatment of myelodysplastic syndromes and subacute myeloid leukemia

Several agents, including arabinosyl cytosine (ARA-C) at a low concentration, can induce leukemic myeloblasts to mature to a variable extent. The therapeutic implications of this observation are worth investigating. A few case-reports have shown that low dose ARA-C can be useful for treatment of the myelodysplastic syndromes (MDS) and of acute myeloid leukemia (AML). However, no information is available yet on the proportion of patients who can be expected to respond. We treated by low dose ARA-C (20-30 mg/sqm/day i.v. or i.m. for 7-10 days) 20 consecutive patients. A complete remission of 5 months was obtained in one of nine cases of subacute myeloid leukemia (SAML). A partial remission (complete normalization of blood counts with a slight excess of marrow blast cells) was obtained twice in one of 11 cases of MDS. An increase of Hb level (more than 11.5 g/dl) was obtained and maintained for 12 months in a case of MDS. A short-lasting increase of granulocyte count was obtained in another two cases of MDS and SAML respectively. It is suggested that low dose ARA-C can advantageously modify the proliferation to maturation imbalance of leukemic cells by slowing down cell proliferation rate. However, the proportion of patients who respond is probably low. This treatment is at a very early experimental stage and should be probably limited to selected cases of MDS and subacute or acute myeloid leukemia.

Acute Disseminated Intravascular Coagulation Syndrome in Cancer Patients

Hemostatic abnormalities are rather frequent in cancer patients either in hematological or in solid tumors. Acute disseminated intravascular coagulation (DIC) is a rare coagulopathy in cancer patients, but when it develops it becomes rapidly fatal. Between June 1988 and December 1992 we observed 8 cases of acute DIC occurring in gastric cancer (4 patients), breast cancer (3 patients) and high-grade non-Hodgkin lymphoma (1 patient). In 3 patients affected by gastric carcinoma, acute DIC was the first manifestation of the presence of the tumor, while in the other patients DIC occurred during the course of the disease. All the patients were treated with heparin, fresh frozen plasma and platelet support, but only in 1 patient was a short duration improvement of clinical conditions and coagulation tests recorded. Acute DIC can be the first manifestation of gastric tumors and the presence of the hemorrhagic syndrome associated with thrombocytopenia, hypofibrinogenemia and fibrin/fibrinogen degradation products should initiate a search for gastric carcinoma.

Intra-arterial hepatic carboplatin-based chemotherapy for ocular melanoma metastatic to the liver. Report of a phase II study.

Aims and Background ocular melanoma tends to metastasize to the liver, sparing for a long time the rest of the organism. Therefore, a regional treatment is especially indicated. Methods eight patients with ocular melanoma metastatic to the liver were treated with intraarterial hepatic carboplatin-based chemotherapy at the dose of 300 mg/m2 once every two weeks at an outpatient clinic. All the patients were submitted to laparotomy with surgical implantation of an arterial port device through the gastroduodenal artery. Results the overall response rate was 38% with a median survival time of 15 months. The regimen was well tolerated and the principle toxicity was myelosuppression; any instance of hepatic and/ or cholangitic damage was reported. Conclusions Carboplatin seems suitable for intraarterial hepatic chemotherapy and active in ocular melanoma metastic to the liver.

Breast metastasis from gastric signet ring cell carcinoma, mimicking inflammatory carcinoma. A case report.

We report a case of breast metastasis of signet ring cell gastric cancer clinically presented as a primary inflammatory carcinoma. Metastases to the breast are uncommon; review of the literature demonstrated only 300 cases. The clinical and radiographic features of the metastatic lesion were unlike those reported in the literature. Although a primary signet ring cell breast carcinoma was described, the pathologic patterns of the breast lesion, here reported, lead us to conclude this was a metastasis and not another primary tumor.

Treatment of primary or metastatic pleural effusion with intracavitary cytosine arabinoside and cisplatin: A phase II study

Thirty-three patients with microscopically verified primary or metastatic malignant pleural effusion were studied: 7 had malignant mesothelioma and 26 metastatic pleural disease. The treatment was based on biochemical and clinical studies which show a synergy between cytosine-arabinoside (Ara-C) and cisplatin. These drugs were instilled in the pleural cavity at the dose of 100 mg for Ara-C and 100 mg/m2 for cisplatin. The cavity was drained after 4 h. If it was possible, the treatment was repeated weekly for 3 times and, after a 6-week rest, it could be started again with the same schedule. The overall response rate (complete plus partial remissions) was 74%. Toxicity was mild or moderate. We conclude that the combination of Ara-C and cisplatin is well tolerated and produces a high response rate in the treatment of malignant pleural effusions.

PRIMARY PULMONARY HIGH GRADE NON-HODGKIN'S LYMPHOMA IN AN ELDERLY PATIENT. A CASE REPORT

An 82-year-old non-smoker female was admitted with cough, fever and poor general health. Radiological examination revealed a right parahilar mass and a transbronchial biopsy confirmed the presence of a tumor. Immunohistochemical analysis established the diagnosis of high-grade primary pulmonary lymphoma. The rare nature of this disease, its non-specific clinical presentation and particular prognosis, also in elderly patients, are discussed in this article.

Epirubicin, cisplatin and continuous infusion 5-fluorouracil (ECF) in locally advanced or metastatic gastric cancer: a single institution experience.

Aims and Background The role of chemotherapy in locally advanced or metastatic gastric cancer has been controversial, but chemotherapy has recently been shown to relieve tumor-related symptoms, improve quality of life and prolong survival when compared with best supportive care. Furthermore, palliative chemotherapy is also cost-effective. “Second-generation” combination chemotherapy regimens were developed in the 1980s with high activity in advanced or metastatic gastric cancer (EAP, FAMTX, PELF, ECF). In randomized studies, EAP demonstrated no difference in activity but a significantly higher overall toxicity and toxic death rate than FAMTX, and the ECF (epirubicin, cisplatin, 5-fluorouracil) regimen gave a survival and response advantage, tolerable toxicity, better quality of life and was more cost-effective than FAMTX. Methods Sixty patients with locally advanced or metastatic gastric cancer were treated with the ECF regimen (21 weeks of 5-fluorouracil given by continuous infusion through a central line at 200 mg/m2 for 24-hr combined with cisplatin at 60 mg/m2 iv and epirubicin at 50 mg/m2 iv beginning on day 1 and repeated every 3 weeks for 8 courses). There were 42 males and 18 females, with a median age of 64 years (range, 40-74). The median performance status was 1. The histologic type was adenocarcinoma in 44 patients and undifferentiated carcinoma in 16 (27%). Three patients had locally advanced disease (5%) and 57 had metastatic disease (95%). Seven patients (12%) had received prior chemotherapy for advanced disease. Results All patients were assessable for toxicity and 55 for response (5 had insufficient treatment). Toxicity was mild or moderate, and there was no toxic death. Incidence of WHO toxicity ≥ 2 was nausea and vomiting in 3%, mucositis in 3%, leukopenia in 7%, anemia in 3%, and thrombocytopenia in 2%. Port-a-Cath toxicity was thrombosis in 4, dislocation in 2 and infection in 3 patients. Seven complete responses and 13 partial responses (overall response rate, 36%) were achieved, with a response rate of 39% in untreated and 17% in pretreated patients. Nine patients (16%) had stable disease and 26 (47%) progressive disease. Most patients felt symptomatically improved on ECF. Conclusions Our study confirms that the ECF regimen has a favorable pattern of toxicity and is feasible on an outpatient basis. However, it did not confirm the high response rate reported in other phase II trials.

CEOP regimen in the treatment of advanced low-grade non-Hodgkin's lymphomas: preliminary report.

Between March 1987 and December 1988, 30 previously untreated patients with low-grade non-Hodgkins lymphomas (NHL), according to the Kiel classification, were treated by a combination of therapy including cyclophosphamide, epirubicin, vincristine, and prednisone (CEOP). Eighteen patients (60%) achieved a complete pathologic remission, and 8 patients (26.6%) had a partial response with a reduction of more than 50% of tumor-related manifestations. Four patients (13.4%) were primary resistant to CEOP. The overall survival was 96.6% with a median follow-up of 25 months from the diagnosis; none of the patients who achieved complete response relapsed at a median follow-up of 21 months from the completion of treatment. Clinical and hematologic toxicities were irrelevant. This regimen was effective in inducing a good remission rate of low-grade NHL, but a longer follow-up for definitive conclusions is warranted.

Carboplatin and etoposide in an out-patient schedule for the palliation of advanced non-small-cell lung cancer.

Aims and background In Western countries, non-small-cell lung cancer is the most important cause of cancer-related death. To date, medical treatment for advanced stages remains of a palliative nature. Methods Forty-four patients with advanced non-small-cell lung cancer were treated in a phase II study with carboplatin and etoposide (each at 60 mg/m2 daily) in a 5-day schedule. Among 44 patients, 18 (40%) had stage IIIB disease and 26 (60%) had stage IV disease. Results Treatment was well tolerated, and the only significant side effect was alopecia. The overall response rate was 27% with 2 complete remissions; median survival time was 10.4 months. One of the 2 patients achieving a complete remission was still alive and disease free at 36 months from the start of therapy. An improvement of performance status was observed in 22 patients (50%). Conclusions The combination of carboplatin and etoposide using this schedule appears to be well tolerated and has some activity in the palliation of advanced non-small-cell lung cancer.

Design and architecture in oncology as supportive care for cancer patients.

their patients during their stay in hospital caused by the cold, impersonal hospital environment which does absolutely nothing to alleviate the physical and mental suffering of these gravely ill patients; on the contrary, it exacerbates their condition. Recent medical and psychological thought, together with a changing cultural sensibility and an increased awareness of the fundamental needs of patients, have led to the designing of projects aimed at humanizing medical institutions. At first glance this kind of concern may seem paradoxical. The ancient “hospitalitas”, which was consolidated in the Middle Ages into a place of treatment to receive pilgrims or entire populations struck by famine and epidemics, was characterized as a place to relieve pain of the body and the spirit and this objective has remained through the centuries until today. It is therefore legitimate to ask why hospitals today are perceived as places where long-term patients are depersonalized and where they lose those important points of reference relating to their individual identities. It is not easy to find satisfactory answers. Maybe a correct analysis should take other aspects of our lives into account such as the social and cultural transformations we have lived through and continue to experience throughout our existence. Opinions vary greatly. There is, however, wide agreement on the necessity to develop programs and carry out research which would once again make our medical institutions “liveable”. Although there are many reasons for promoting this objective, there are probably only two principal ones. Firstly, by definition the hospital is a place for sick people and time spent in hospital usually means a loss of autonomy for patients. Because of the organizational needs of the hospital, patients are usually subjected to routines and environments which are totally alien to their normal habits and time schedules; waking up, going to sleep and eating meals at different times from normal, loss of space or having to share space with others, and inactivity. Time slows proportionally to the passivity of letting the hours and minutes go by. Making plans or organizing for the future is usually non-existent or reduced to a minimum. The environment, or better, the space, which is almost always characterized by inexpressive cold and monotonous colors on the walls of the rooms, corridors and waiting rooms, induces patients to withdraw even more into themselves and dwell on their worries and anxieties regarding their state of health. The second reason is instead a consequence of the technological transformations which have taken place in the field of medicine and which have inevitably impoverished the doctor-patient relationship (CT scan, MRI, PET, etc.). Symptomatology, which at one time was the basis of a possible diagnosis, has gradually faded, often reduced to a quick listen to heartbeat and chest murmur and an abdominal examination. Time shared by doctor and patient is continually reduced, above all because time dedicated to meeting and talking, to gradually giving and receiving complete information, and to positive communication tends to be compressed by productivity needs and requirements that are in no way compatible with the dramatic situation the patient is going through in certain moments. In order to modify this tendency (apart from projects to improve the psychological aspects of communication, the patient-doctor-hospital relationship, and generally how to receive the patient in hospital), the possibility of using different artistic forms has been studied. Some of these ideas have already been experimented in different fields of medicine, for example in pediatrics and psychiatry as supportive care for patients and as ways of managing time and space in a more constructive fashion. It is, however, more complicated to consider the architectural restructuring or planning of new cancer units or day hospitals. The literature on this subject is sparse but we are beginning to see a gradual tendency to focus more attention on the problem. Architecture and design, particularly in this field, must address the impact that artistic expression can have on the patient’s general physical and psychological condition; living through the experience of a grave illness, the fear of pain and suffering, the fear of death. Space, in terms of light, materials, shapes and dimensions, must consider these difficult and painful feelings Tumori, 93: 645-646, 2007