A phase II study of 5-fluorouracil and high-dose folinic acid in combination with cyclophosphamide and mitoxantrone for advanced breast cancer.

38 patients with advanced breast adenocarcinoma were treated in a phase II study with 5-fluorouracil and high-dose folinic acid combined with cyclophosphamide and mitoxantrone. 6 patients had received prior chemotherapy for advanced disease, all with an anthracycline-containing regimen. Treatment was generally well tolerated. The most common side-effect was myelosuppression, with 1 toxic death due to leukopenia-related sepsis. 1 patient developed severe congestive heart failure 12 months from the end of therapy. 36 patients were evaluable for response. The overall response rate was 55%. Median duration of response was 8 months and median survival time was 16 months. This regimen warrants further investigations.

Gastrointestinal autonomic nerve tumor: case report and review of the literature.

Gastrointestinal autonomic nerve (GAN) tumor is an uncommon specialized form of gastrointestinal stromal tumor (GIST). We report the case of a 46-year-old man affected by this tumor. The neoplasm arose from the sigmoid colon. The patient underwent surgery but eight months later an omental relapse occurred. A second laparotomy was successfully performed and the patient is free of disease at 21 months of follow-up. To our knowledge this is the first case of a large bowel GAN tumor described in the literature.

Primary non-Hodgkin lymphomas of the gastrointestinal tract: analysis of 41 cases.

Forty-one patients suffering from primary non-Hodgkin lymphomas of the digestive tract have been observed over a period of 15 years. The primary sites were: the stomach in 27 cases, the small bowel in 8, the ileocecal region in 5, and the mesentery in 1. Patients were staged according to the modified Ann Arbor staging system proposed by Mushoff (20). Four kinds of management were employed: 1) surgery alone; 2) surgery and radiotherapy; 3) surgery, radiotherapy and chemotherapy; 4) surgery and chemotherapy. One patient was treated by chemotherapy alone. Radiotherapy was administered postoperatively and chemotherapy after or during radiotherapy. Generally, 2 opposed fields largely encompassing the tumor area and lomboaortic nodes if necessary, up to 25-30 Gy to the midline, were employed, with a booster dose up to 40-45 Gy to the involved area. Total abdominal irradiation was never employed. No clear difference emerged in survival rate nor in relapse-free survival among the four subgroups, but patients who underwent complete resection fared better than incompletely resected patients. However, these two subgroups were not homogeneous. A clear difference in survival rate did not emerge between patients treated or not with postoperative chemotherapy, whereas patients who relapsed after complete remission or those who never had complete remission had a poor prognosis.

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 > or = 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.

Four years experience of primary intra-arterial chemotherapy (PIAC) for locally advanced and recurrent breast cancer.

AIMS: To find a means of achieving operability very quickly without the additional discomfort of prolonging systemic chemotherapy. To improve the patient's quality of life by obtaining quick tumor reduction and decreasing systemic toxicity. MATERIALS AND METHODS: From January 1991 to January 1995, 13 patients with locally advanced breast cancer (LABC) and 8 patients with recurrent breast cancer (RBC), were treated by transfemoral Seldinger technique, with the catheter tip placed into the subclavian artery at the basis of the internal mammary artery. The patients received 5-fluorouracil (5FU) 1000 mg, epirubicin (EPI) 30 mg/m2, mitomycin (MMC) 7 mg/m2 over an infusion for 30 minutes. The cycle was repeated every two weeks for three times. RESULTS: The overall response rate was 62%. Stage IIIb and RBC patients had a response rate of 100% and 25% respectively. In respondent patients a measurable response was seen after the first cycle. Ten patients were radically operated. After a media follow-up of 21 months, the overall survival is 52% at 48 months (68% at 48 months and 65% at 34 months for stage IIIb and RBC patients respectively). CONCLUSIONS: PIAC is feasible and effective. In LABC patients it reaches 100% of response rate. Systemic toxicity was absent and the local one was mild. The interval between the starting of PIAC and operation is short. There was an optimal compliance of the patients.

[Pulmonary metastasis from an eccrine carcinoma: thoracic perfusion with the aorto-caval stop-flow technique. Description of a clinical case]. / Metastasi polmonari da carcinoma eccrino: perfusione toracica con tecnica dello stop-flow aorto-cavale. Descrizione di un caso clinico.

A case of a 64-year-old man with eccrine carcinoma arising from hand skin is reported. At the time of diagnosis he showed bilateral pneumonic metastases. Although the patient underwent two systemic chemotherapy lines, he showed further progressive disease of the lung. For this reason a third chemotherapy line was started through thoracic stop-flow infusion. In this way, a five month stable disease had been achieved. The patient died 7 months later for progressive disease. The rarity of this disease, the uncertain treatment, the feasibility and efficacy of thoracic stop-flow infusion are underlined and further studies are suggested.

[Does locoregional chemotherapy improve survival in patients with non-resectable pancreatic carcinoma? Results of an open controlled study]. / La chemioterapia locoregionale migliora la sopravvivenza dei pazienti affetti da carcinoma pancreatico non resecabile? Risultati di uno studio aperto, controllato.

About 90% of patients suffering from pancreatic carcinoma are diagnosed with disease that is not amenable to surgical intervention due to local infiltration or the presence of hepatic metastases. Palliative intra-arterial chemotherapy was developed to improve the response in these patients by increasing the antiblastic dose and minimizing the side effects. The aim of this study is to evaluate the efficacy of this treatment comparison to a control group. From December 1994 to February 1997, 135 patients with ductal carcinoma, in whom 68 were stage III and 67 stage IV, with a median age of 63.3 years (range 38.4-79), were enrolled in an open study. Sixty four patients were subjected to a median of 3.5 cycles, according to intra-arterial FLEC protocol. Four patients had a partial response (6.3%), 27 enjoyed a stabilization of their disease (42.2%) and 13 showed disease progression (20.3%). The toxicity was mild. The overall survival was 8.3 months, better in the treated group (9.6 months) in respect to the control one (7.1 months), although this was not statistically significant. The treatment reported here, therefore, does not seem to change the prognosis of patients affected by no resectable pancreatic carcinoma, but it may demonstrate good tolerability and minimal toxicity.

[Extraskeletal diffusion of multiple myeloma. A clinico-pathological description of 4 cases]. / Diffusione extrascheletrica nel mieloma multiplo. Descrizione clinico-patologica di quattro casi.

The authors describe 4 cases of multiple myeloma that developed one or more extraskeletal localizations. They have evaluated the relation between the onset of the extraskeletal localizations and the following myeloma characteristics: tumor burden, clinical phase, chemotherapy response, prognostic significance. All the patients showed these localizations in a plateau phase of myeloma. None of the patients had fever, pancytopenia and in no one the performance status worsened. All patients obtained at least a partial reduction of the localization and only the patient with the retro-orbital localization, got worse and died for myeloma. The other three patients are alive and do not show any sign of progression.

[Current approaches in the medical treatment of advanced ovarian carcinoma]. / Attuali orientamenti nella terapia medica del carcinoma ovarico in fase avanzata.

Ovarian cancer is most frequently diagnosed at an advanced stage. In recent years there has been intense interest in the chemotherapy of this disease. About cisplatin, the most active agent in the treatment of advanced ovarian cancer, some questions are only partially answered, as the optimal dose, the duration of treatment, the role of ciplatin-based two-, three-, or four-drug regimens, the role of intraperitoneal therapy, the use of old and new drugs in cisplatin-resistant patients. Carboplatin is currently the most important cisplatin analogue with a toxicity pattern very different from that of the parent compound, but, up to date, the combination of these two drugs does not seem to be any better than standard chemotherapy. Among new drugs, three deserve particular attention: taxol, a natural produce from the bark of the Pacific yew Taxus brevifolia, taxotere, a taxoid obtained by semisynthesis from the needles of the European yew Taxus baccata and gemcitabine, a cytostatic agent with a close resemblance to cytosine-arabinoside. Anyway, new approaches must continue to be sought too: among these, probably gene therapy may offer the best mechanism to overcome both intrinsic and acquired drug resistance.

[Prognostic factors in breast carcinoma with negative axillary lymph nodes]. / Fattori prognostici nel carcinoma mammario con linfonodi ascellari negativi.

Conventionally, tumor size, axillary lymph nodes status, histologic type and grading, proliferative activity, steroid receptors have been used to predict the natural history of breast cancer. In node-negative patients with breast cancer it is most important to identify biological markers that can predict the risk of systemic relapse. These features have been used to allow selection of the best treatment. In this paper we describe the prognostic significance of new tumoral markers in breast cancer patients without axillary involvement. We analyze the prognostic role and the correlation with response to treatment of these parameters: ploidy, oncogenes, p53, epidermal growth factor receptor and cathepsin D.

[Oropharyngeal and rhinopharyngeal carcinomas in patients treated for non-Hodgkin's lymphoma]. / Carcinoma dell'oro- e del rinofaringe in pazienti trattati per linfoma non-Hodgkin.

The authors describe two cases of nasopharynx and oropharynx carcinomas in treated non-Hodgkin lymphoma's patients. They evaluate pathogenetic hypotheses related to lymphoma, its treatment and some exogenous factors like smoke, alcohol, Epstein-Barr virus.

[Lymphoma of the bladder. Description of 2 cases and review of the literature]. / Linfomi a localizzazione vescicale. Descrizione di due casi e revisione della letteratura.

Two case reports and review of the literature. The authors describe one case of primary lymphoma and one case of secondary lymphoma of the bladder. They evaluate the differences, underline the rarity of the primitive type and make a review of the literature.

[Systemic mastocytosis. A review of current diagnostic and therapeutic approaches]. / La mastocitosi sistemica. Revisione degli attuali approcci diagnostico-terapeutici.

Mastocytosis is a heterogeneous group of disorders characterized by abnormal growth and accumulation of mast cells in skin, bone marrow, bone, gastrointestinal tract, liver, spleen and lymph nodes. Today, regarding its biological features, mastocytosis (with or without myeloid accompanying disorders) is considered to be a hematologic disease. The classification proposed by Metcalfe in 1991 is the most useful in caring for patients with mastocytosis. In this classification 4 groups are described: 1) indolent mastocytosis with or without extracutaneous involvement; 2) systemic mastocytosis with an associated hematologic disorder; 3) aggressive mastocytosis; 4) mast-cell leukemia. Cutaneous mastocytosis typically presents as urticaria pigmentosa or diffuse cutaneous mastocytosis and these patients usually have a benign course. On the contrary, systemic mastocytosis is a disease with an increased risk to develop an aggressive hematologic disorder. In these patients a second hematologic process, such as myeloproliferative or myelodysplastic syndrome or acute leukemia, may occur. These patients often present without skin involvement and they have a very poor prognosis. Mast cell is a medium-sized granulated cell releasing chemical mediators (histamine, heparin, protease and cytokines). Mast cells originate from pluripotent hemopoietic progenitor cells that express the CD34 antigen. Mast cells are present in the bone marrow and are distributed throughout the connective tissues. Recently a mast-cell growth factor (MGF) has been identified. Clinical symptoms occur from the release of chemical mediators and the pathologic infiltration of cells. Although no effective therapy for patients with Mastocytosis is known, some patients may benefit from corticosteroid and interferon alpha treatment. The present article gives an overview of current knowledge about the biology, heterogeneity and treatment of human mastocytosis.

[Primary non-Hodgkin's lymphoma of the bone. Description of 2 cases]. / Linfomi non Hodgkin primitivi dell'osso. Descrizione di due casi.

Primary bone non Hodgkin's lymphomas (PBL) are approximately 5% of extranodal lymphomas and 5% of all primary bone tumors. A standard treatment has not been codified yet. The most received only radiotherapy but recently it was introduced combined modality treatment with radiotherapy plus chemotherapy or chemotherapy alone. The authors describe two cases of high grade PBL that received combined treatment with chemotherapy (VACOP-B regimen and monochemotherapy with mitoxantrone respectively) and radiotherapy. The patients achieved complete remission and up to day are alive and disease free at 33 and 15 months from the diagnosis respectively.

[Testicular lymphomas. A clinico-pathological study of 5 cases and a review of the literature]. / I linfomi testicolari. Studio clinico patologico di 5 casi e revisione della letteratura.

The authors describe five consecutive patients with testicular non Hodgkin lymphoma, evaluate the clinical and histological characteristics and underline the importance of a chemotherapy approach both at diagnosis and at relapse. A review of the literature is carried on and particularly about the prognostic factors, the correlation with Ebstein Barr virus and the more recent integrated therapeutical approaches.

[Combined intra-arterial locoregional and systemic treatment of nonresectable hepatic metastases of colorectal carcinoma]. / Trattamento combinato locoregionale intra-arterioso e sistemico delle metastasi epatiche non resecabili da carcinoma del colon-retto.

Intra-arterial hepatic chemotherapy (LAHC) results in significantly higher response rate than the best systemic treatment of liver metastases from colorectal cancer, but no survival advantage has to date shown because of extra-hepatic progression. From June 1991 to December 1994, twenty patients with hepatic metastases from colorectal cancer were enrolled. All patients underwent laparotomy for the placement of an intra-arterial catheter into the gastroduodenal artery connected with a subcutaneous port. All patients underwent cholecystectomy and biopsy of liver lesion to confirm metastatic disease. Locoregional schedule was: 5-fluorouracil (5FU) 500 mg/sqm, epirubicin (EPI) 13 mg/sqm, mitomycin-C (MMC) 7 mg/sqm, in bolus every 3 weeks. Systemic therapy consisted of leucovorin 500 mg/sqm, over 2 hours and 5FU 600 mg/sqm in bolus every week. Treatment was planned over a six month period. The complete response (CR) plus partial response (PR) rate was 50% of the entire group. The median survival was 18 months and 1- and 2- and 3-year survival rates were 71%, 38% and 20% respectively. Prior to chemotherapy, LDH value and % of liver involvement were the only significant prognostic parameters. Toxicity was absent or mild and no patient stopped treatment because of side effects. Combined systemic and IAHC is an effective treatment for liver metastases from colorectal cancer, with a mild or moderate toxicity. However, more trials are needed, to improve the control of the extrahepatic disease.

[Cisplatin and cytosine arabinoside (ARA-C) for the therapy of primary and secondary pleural neoplasms]. / Cisplatino e citosina arabinoside (ARA-C) nella terapia delle neoplasie pleuriche primitive e secondarie.

15 patients with primary or metastatic pleural effusion were studied: 2 had diagnosis of malignant mesothelioma and 13 of metastatic pleural disease. The treatment used was based on in vitro and in vivo studies which show a synergy between ARA-C and Cisplatin. These drugs were instilled in pleural cavity at the dose of 100 mg./m2 for Cisplatin and 100 mg. for ARA-C. The cavity was drained after 4 hours. The treatment was repeated weekly. All patients had not been previously treated with loco-regional therapy. The response rate was 93% with 10 loco-regional complete remissions (66%). The two patients with malignant mesothelioma achieved a complete remission. The overall toxicity was acceptable. We conclude that combination of Cisplatin and ARA-C is well-tolerated and produces a very high response rate in the treatment of malignant pleural effusions.

[Intra-arterial chemotherapy in locally advanced or recurrent breast neoplasms]. / La chemioterapia intraarteriosa nella neoplasia mammaria localmente avanzata o recidiva.

Intraarterial chemotherapy is studied as an alternative procedure for the neoadjuvant treatment of locally advanced and recurrent breast cancer. Our study was aimed at investigating the feasibility, the toxicity and the local response rate of an intraarterial chemotherapy regimen including 5-fluorouracil, epirubicin and mitomycin. These drugs were administered angiographically into the subclavian and internal mammary arteries ipsilateral to the lesion. We treated 20 women with a median age of 58 years (range: 42-74 years); 12 patients had locally advanced breast cancer with a median tumor size of 12 cm (range: 6-20 cm) and 8 patients exhibited cutaneous, thoracic or axillary recurrences, with a median lesion size of 6 cm (range: 3-12 cm). In all, we administered 54 cycles of chemotherapy drugs (mean: 2.7 cycles a patient). Most patients were submitted to selective catheterization of the internal mammary artery (44/54 cycles); all the drugs were injected into the subclavian artery only when catheterization of this vessel was unfeasible. No angiography-related toxicity was observed. No systemic, particularly hematological, toxicity was observed. Four patients exhibited skin erythema in the feeding region of the internal mammary artery, 2 hemialopecia, 1 cutaneous steatonecrosis and 1 transient hemiplegia. We obtained 1 complete remission and 11 partial responses, with 60% overall response rate (12/20 patients). All the patients with locally advanced breast cancer had an objective response and the mean interval between the start of therapy and radical mastectomy was only 49 days. In conclusion, intraarterial chemotherapy for locally advanced or recurrent breast cancer is a feasible and well-tolerated tool which needs further studies, particularly to assess its efficacy.

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.

Stomach preservation in low- and high-grade primary gastric lymphomas: preliminary results.

BACKGROUND: The optimal management of primary gastric lymphomas has yet to be defined. In the past surgery was advocated as the optimal first step for patients with PGL. Recently, an increasing number of studies suggest that chemotherapy is as effective as surgery. METHODS: Fourteen patients with PGL were treated with chemotherapy alone. For patients with low-grade lymphoma, chemotherapy consisted of mitoxantrone 5 mg/sqm on days 1 to 3. Treatment courses were administered every 3 weeks up to a maximum of 6 cycles. Patients with high-grade lymphoma received chemotherapy according to the CHOP schedule every 4 weeks up to a maximum of 6 cycles. Two patients with high-grade lymphoma were treated as low-grade lymphoma patients (one because of age and poor performance status, the other because she refused chemotherapy that would cause hair loss). Two patients with low-grade lymphomas who did not respond to mitoxantrone were crossed over to CHOP. RESULTS: All patients were evaluable for toxicity, 13 for response to therapy and survival. Toxicity was mild or moderate. Neither perforation nor hemorrhage was observed. Eleven patients achieved a complete remission (85%), 1 a partial remission (7.5%) and 1 underwent disease progression (7.5%). At a median follow-up of 12 months (range 4-44 months) all complete responders are alive and disease free. CONCLUSIONS: Although the number of evaluable patients is too small to draw any final conclusions, chemotherapy seems to be as effective as surgery in PGL, and stomach preservation improves the quality of life of the patients.