Second line therapy with weekly low-dose docetaxel for pretreated non-small-cell lung carcinoma patients: a multicenter Italian phase II study.

Docetaxel is one of the most active drugs in second-line therapy for non-small-cell-lung-carcinoma (NSCLC). The aim of this multicenter study was to evaluate the safety and efficacy of weekly low-dose docetaxel. Forty-two patients with advanced NSCLC pretreated with cisplatinum-based chemotherapy were enrolled. Docetaxel was administered at a dose of 25 mg/m(2) weekly for 12 consecutive weeks. A total of 386 doses were given with a median number of 10 doses per patient (range: 3-12). Treatment showed low incidence of hematologic toxicity and modest non-hematologic toxicity. An episode of grade 4 thrombocytopenia was reported but no episodes of grade 3 or 4 neutropenia. Most frequent non-hematologic toxicities were asthenia and alopecia. Response rate was 10.5% and median survival time (MST) was 12.8 weeks. Weekly treatment with 25 mg/m(2) docetaxel for 12 consecutive weeks appears to be a feasible and active regimen with mild toxicity in heavily pretreated NSCLC patients.

Tamoxifen alone versus adjuvant tamoxifen for operable breast cancer of the elderly: long-term results of the phase III randomized controlled multicenter GRETA trial.

BACKGROUND: To evaluate the efficacy of tamoxifen as primary treatment in women aged over 70 years with operable breast cancer versus surgery followed by adjuvant tamoxifen. PATIENTS AND METHODS: Patients randomly received tamoxifen alone (160 mg day 1, then 20 mg/day) for 5 years or surgery followed by tamoxifen (20 mg/day) for 5 years. Overall survival was the main study end point; secondary objectives included breast cancer survival and local control of the disease. RESULTS: Between 1987 and 1992, 239 patients were assigned to surgery plus tamoxifen and 235 to tamoxifen alone. Treatment arms were comparable for tumor size, clinical nodal status and performance status. At a median follow-up of 80 months 274 patients had died. No difference between groups had emerged in overall and breast cancer survival. There were 27 local progressions in the surgery plus tamoxifen group and 106 in the tamoxifen-alone group (P = 0.0001). In the surgery plus tamoxifen group, no difference in overall survival had emerged according to the extension of operation. CONCLUSIONS: The long-term results of the study confirm the 3-year interim analysis already reported. Surgery (radical or minimal) followed by adjuvant tamoxifen does not modify overall and breast cancer survival as compared with tamoxifen alone in early breast cancer of older women. Because of the high rate of local progressions with tamoxifen alone, minimal surgery followed by tamoxifen appears to be the appropriate treatment in such patients. More extensive surgery is not useful. Tamoxifen alone is an adequate alternative treatment in very old or frail patients.

[Ulcero-necrotic and lymphoproliferative naso-paranasal lesions in cocaine abuse]. / Lesioni ulceronecrotiche e linfoproliferative naso-paranasali da abuso di cocaina.

In this work are reported two clinical cases of cocaine abusers with destructive lesions of nasal-paranasal cavities. The clinical presentation and the absence of a positive history of drug addiction led to a differential diagnosis between lymphoma, idiopathic median line granuloma and Wegener granulomatosis. Biochemical and serological examinations did not prove conclusive. The diagnosis was finally formulated on the basis of the documented presence of cocaine in the biological fluids. Emphasis is placed in the difficulty of obtaining a reliable case history in this type of patients. Moreover, the Authors point out that it is advisable to test for drugs in the biological fluids prior to undertaking time-consuming diagnostic procedures for pathologies which are extremely rare in the West countries.

Pulmonary asbestosis associated to pleural non-Hodgkin lymphoma.

We describe herein a case report of a patient affected by pulmonary asbestosis who developed a non-Hodgkin lymphoma originating in the pleura. The case is unusual for the uncommon site and because the chronic antigenic stimulation by asbestos bodies may have locally promoted an immunologic derangement.

Complications of subcutaneous infusion port in the general oncology population.

Subcutaneous infusion ports (SIPs) represent a valid method for long-term chemotherapy. The SIPs have several advantages over other methods of venous access: they are easy to implant under local anaesthesia, have less discomfort for the patients, allow low costs, can be implanted in day hospital, and can be managed ambulatorily. However, SIPs have delayed complications, frequently related to clinical conditions of the neoplastic patients, and immediate complications, often due to the placement technique. From March 1992 to March 1997 we placed, under local anaesthesia and under fluoroscopic control, 102 SIPs in 99 general oncology patients for long-term chemotherapy (88% solid, 12% haematological tumours). The percutaneous venous access devices were in the subclavian vein in 96% of the cases and in the internal jugular vein in 4% of them. Immediate complications were: 1 haemopneumothorax, which required thoracic aspirations and two blood transfusions, 1 loop of the tunneled part of the catheter without alterations in SIP function, and 1 left jugular thrombosis in a patient with subclavian veins already thrombosed. The venous access was in the subclavian vein in the first 2 cases, and it was not necessary to suspend the therapeutic program. In the third instance, implanted in jugular vein, it was necessary to remove the SIP. Delayed complications were: 1 necrosis of the skin over the port, 1 infection of subcutaneous pocket, 2 infections of the system, 1 catheter deconnection, and 3 catheter ruptures with embolization of the catheter tip. The SIPs were removed in all cases but 1 in whom infection was successfully treated by appropriate antibiotic therapy. Embolization of the catheter required removal from the pulmonary artery under fluoroscopic guidance in the cardiac catheterization laboratory. In conclusion, infection and thrombosis are the two major complications of SIP in general oncology patients. In these cases it is not necessary to remove systematically the system, but a correct therapy (antibiotic, fibrinolytic agents) can be utilized with good results. The catheter rupture is often due to the wear over the costoclavicular angle. The interventional radiology is the method of choice in the treatment of the catheter embolization by rupture or dislocation. The experience of the surgical and nursing staff is probably the most important factor in decreasing the total rate of complications.

Long-term toxicity in adjuvant treatment with tamoxifen.

Long-term treatment with tamoxifen has produced few side effects, which are generally mild. Of the serious ones, all of them except eye toxicity seem to be related to the molecule's intrinsic mildly estrogen-like action, such as, for example, endometrial carcinoma. This property is also responsible for some favorable clinical effects including a lower risk of osteoporosis and cardiovascular disease. Whether tamoxifen causes neoplastic growth in patients who develop resistance to this drug is still controversial. Further prospective clinical studies are therefore needed to investigate such problems and also to evaluate less frequent side effects. Moreover, decisions on the overall duration of hormone therapy should be based on possible side effects as well as on therapeutic response.

Cis/carboplatin + vinorelbine +/- radiotherapy in stage III and IV non small cell lung carcinoma.

The aim of this study was the retrospective evaluation of the effectiveness of cis/carboplatin + vinorelbine +/- radiotherapy in 118 patients with advanced non small cell lung carcinoma (NSCLC). To evaluate the response, pts were divided into three groups: a) Stage III pts. who received both chemotherapy and radiotherapy treatment (RC + RP = 43.75%, median survival 16.25 months); b) Stage III pts. who underwent only CT because RT was contraindicated (RC + RP = 21.95%, median survival 12.7 months); c) Stage II pts treated with CT alone (RC + RP = 20%, median survival = 12.1 months). Toxicity was mild. The results of the present study, both in terms of response rate and survival, confirm the effectiveness of the combination cis/carboplatin + vinorelbine +/- radiotherapy as palliative treatment of advanced NSCLC.

Randomized phase II noncomparative trial of oral and intravenous doxifluridine plus levo-leucovorin in untreated patients with advanced colorectal carcinoma.

BACKGROUND: Doxifluridine (5-dFUR) is a fluoropyrimidine derivative that has been shown to be active on a variety of solid tumors. The clinical use of intravenous (i.v.) 5-dFUR as a bolus injection or short term infusion has been limited because of its unpredictable severe neurotoxicity. Unlike fluorouracil (5-FU), 5-dFUR is effective when administered orally. METHODS: This randomized, parallel-group, Phase II trial of two schedules of 5-dFUR was conducted between April 1993 and September 1994. A total of 130 previously untreated patients with locally advanced or metastatic colorectal carcinoma were randomized to receive oral levo-leucovorin (1-leucovorin) 25 mg/dose followed by oral 5-dFUR 750 mg/m2 twice daily for 4 days every 12 days (arm A) or i.v. 1-leucovorin 25 mg/dose followed by i.v. 5-dFUR 3000 mg/m2 for 5 days every 21 days (arm B). RESULTS: The two treatment arms were well balanced in terms of age, sex, and disease extension. Metastases were present in more than 90% of the total population, with the liver being the most common site. A median of 7 oral courses (range, 1-15) and 5 intravenous courses (range, 1-9) were administered. Intent-to-treat analysis rate of the randomized patients revealed a response rate of 15% (95% confidence interval [CI], 7-26) in arm A and 41% (95% CI, 29-54) in arm B. However, 7 cases in arm A and 12 in arm B were inadequately treated, and the response rates, according to standard analysis, were respectively 17% (95% CI, 8-28) and 51% (95% CI, 37-65). The median time to treatment failure was 4 months (range, 1-23) and 7 months (range, 1-9), respectively, for the two groups; median survival was 11 months (range, 1-24) in both groups. National Cancer Institute Grade 3 and 4 diarrhea were observed in 25% of the orally treated patients and in 18% of those receiving i.v. treatment. Stomatitis was reported mainly in arm B (15%). Mild and moderate neurotoxicity was observed in 6% of the patients in both arms; no severe neurotoxicity was reported. CONCLUSIONS: 5-dFUR with l-leucovorin, administered either orally or intravenously, produces response rates that are similar to those offered by the regimens containing 5-FU that are usually used to treat advanced colorectal carcinoma. This study documents the good tolerance of the i.v. schedule administered as a 1-hour infusion; furthermore, oral administration seems to be promising and feasible as a home treatment.

[Guidelines for the health protection and safety of workers exposed to antineoplastic drugs]. / Linee guida per la tutela della salute e per la sicurezza dei lavoratori esposti a chemioterapici antiblastici.

The guidelines must guarantee that occupational exposure to antineoplastic chemotherapeutic drugs is kept at the lowest level possible. Occupational exposure to these drugs can involve different categories of workers and different job tasks, such as stocking, preparation, administration, disposal, maintenance of safety cabinets and room cleaning where these activities are performed. Preventive measures should include the institution of "Centralized Units for handling antineoplastic chemotherapeutic drugs", where only specifically trained personnel are employed. Cleaning and decontamination procedures must be easily feasible and specific safety cabinets should be used in the rooms. Personnel must use adequate protective equipment and follow standardized working procedures. Information programs for the personnel should be carried out covering occupational risks, safe preventive measures and the explanation of environmental and biological monitoring.

Efficacy and tolerability of nasally administered compared to parenterally administered metoclopramide in the symptomatic treatment of chemotherapy-induced emesis in cancer outpatients. A controlled clinical study.

The clinical efficacy and tolerability of a new nasal spray formulation of metoclopramide (MTC) was evaluated in terms of its ability to prevent the nausea and vomiting induced by a moderately emetic chemotherapy (cisplatin 20 mg/m2 weekly as radioenhancer+radiotherapy for a fractionated total of 60 Gy) in 12 patients with non-small-cell lung cancer, stage IIIB. The first chemotherapy cycle was administered without any prophylaxis in order to identify those patients who experienced grade 2 nausea and/or vomiting. As prophylaxis during the second cycle, these patients were given MTC 20 mg i.v. at time zero, and MTC 20 mg i.m. after 4 h and 8 h; during the third cycle, they received MTC 40 mg by nasal spray 2 h before chemotherapy, followed by the same dose at 4 h and 8 h. The two prophylactic treatments (parenteral injections and nasal spray) proved to be therapeutically equivalent: complete protection, 6 and 6 patients respectively; major protection, 2 and 3 patients; minor protection, 1 and 1 patient; no protection, 3 and 2 patients. The control of nausea was satisfactory, with 7 and 9 patients respectively experiencing grade 0-1 nausea. Comparative analysis of individual responses confirmed the similar anti-emetic efficacy of the two regimens. No adverse reactions were observed at any time during the course of the study, and all 12 patients judged the acceptability of the new formulation as optimal. It can thus be concluded that the use of metoclopramide nasal spray represents an effective, safe, easily managed and low-cost therapeutic alternative for the prophylaxis and treatment of emesis induced by low-dose chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of neuron-specific enolase, tissue polypeptide antigen, and carcinoembryonic antigen as markers for staging and monitoring response to therapy of lung cancer.

Serum neuron-specific enolase (NSE), tissue polypeptide antigen (TPA), and carcinoembryonic antigen (CEA) were measured in 60 patients with small-cell lung carcinoma (SCLC) and in 94 patients with advanced non-small-cell lung carcinoma (NSCLC) at diagnosis, during induction chemotherapy, and at restaging. At diagnosis, the positivity rates of NSE, TPA, and CEA were 88, 52, and 43% in SCLC, and 20, 62, and 53% in NSCLC, respectively. Serum NSE and TPA levels were significantly higher in extensive than in limited SCLC. TPA and CEA levels were significantly correlated with the extent of NSCLC. NSE and TPA were significantly concordant with the clinical response to initial combination chemotherapy, the former in SCLC, the latter in both SCLC and NSCLC. By discriminant analysis, the presentation levels of the markers were not predictive of response to induction chemotherapy, whereas changes in NSE and TPA levels after the first cycle of chemotherapy were.

Pharmacokinetics and bioavailability of metoclopramide nasal spray versus metoclopramide intravenous in healthy volunteers and cancer patients.

The kinetics and bioavailability of a new formulation of metoclopramide (CAS 364-62-5) nasal spray (MTC NS) were assessed in two separate studies versus the same drug administered intravenously (MTC IV) according to a balanced-block design where each study subject served as his own control. The first study involved 10 healthy subjects, each receiving metoclopramide NS 20 mg (one 10-mg puff per nostril) and metoclopramide IV 20 mg on two trial days separated by a 7-day washout period. On both occasions, blood samples were obtained at time 0 and at 20, 40, 60, 120, 150, 210, 280 and 360 min of dosing. Metoclopramide concentrations were assayed in plasma by HPLC. The second study involved 10 patients of oncologic domain, scheduled to receive mildly emetic chemotherapy regimes. The experimental design was similar to the one above except that blood was sampled at 0, 20, 40 and 60 min and again at 2, 3, 4, 6, and 8 h of dosing. All healthy subjects completed the trial without experiencing any adverse or untoward events; in the group of cancer patients, one subject dropped out after the nose spray treatment when he was removed to another department. This patient was replaced by another, and included in final data analysis only for the segment of treatment actually received. Metoclopramide kinetics after intravenous dosing were in good agreement with known data for the active substance, with no meaningful differences between healthy subjects and cancer patients. With MTC NS administration there was only a slight but significant difference of Cmax, being lower in the cancer patient group (p < 005).(ABSTRACT TRUNCATED AT 250 WORDS)

Concurrent carboplatin (CBDCA), vindesine (VDS) and radiotherapy in stage III non small cell lung cancer (NSCLC).

AIMS: Aim of the study was to test, in a cooperative and prospective trial, the effectiveness and feasibility of a chemoradio-therapy program in stage III non small cell lung cancer (NSCLC). METHODS: The schedule consisted in carboplatin (CBDCA) 150 mg/m2/iv on days 1, 3, 5 and vindesine VDS 2.5 mg/m2/iv on days 1, 8, 15, 22 every 4 weeks for 2 cycles followed by radiotherapy 60 Gy with CBDCA 50 mg/m2 weekly as radioenhancer. The same schedule was proposed as neoadjuvant treatment in 10/47 patients (stage III A) and as exclusive treatment in 37/47 (stage III B) admitted patients. RESULTS: In the neoadjuvant subgroup partial remission was obtained in 5/10 patients, and 3 of them underwent surgery with consequent CR. In the stage III B subgroup, 2 complete remissions were obtained (survival 14 and 9+ months). Toxicity was mild. CONCLUSIONS: Our results confirm the feasibility of the schedule in stage III NSCLC.

Prospective randomised trial comparing fluorouracil versus doxifluridine for the treatment of advanced colorectal cancer.

Doxifluridine (dFUR) is a fluoropyrimidine derivative that has shown activity on a variety of solid tumours. The purpose of this study was to compare its therapeutic effect with a standard fluorouracil (FU) regimen in patients with locally advanced or metastatic colorectal cancer. 222 previously untreated patients were randomised to receive dFUR (4000 mg/m2) or FU (500 mg/m2) daily for 5 days every 28 days. The primary tumour originated in the colon in two-thirds of the cases in both groups; approximately 90% of patients had metastatic extension, and liver involvement was present in 69% of the patients in the dFUR and FU groups. A good performance status (ECOG 0-1) was recorded in 90% of cases in both arms. A median of five cycles was administered to the patients (range 1-12). Only one partial response among 110 patients in the FU arm and one complete response and five partial responses out of 112 evaluable patients in the dFUR group were observed. Time to progression was significantly longer in the dFUR group (P = 0.02); overall survival, while longer in the dFUR arm (48 weeks vs. 39 weeks), was not significantly so (P = 0.08). Toxicity was acceptable in both arms, although grade 3-4 neurological side-effects and leukopenia were more common after dFUR infusion. Despite the low response rate, our results indicate that dFUR may be a superior alternative to FU. The possibility of enhancing significantly the activity of dFUR with biochemical modulators should be further investigated.

Treatment of carcinoid syndrome with recombinant interferon alpha-2a.

The prognosis and the quality of life of patients with carcinoid tumors is related either to symptoms from the substances secreted or to progressive tumor growth. Medical treatment with cytotoxic agents is of marginal value for increasing life expectancy and reducing clinical symptoms. Recent studies with interferon have shown interesting results. In the present investigation, 22 patients with carcinoid tumors and syndrome were treated with recombinant interferon alpha-2a (r-IFN alpha-2a) at the dose of 6 x 10(6) IU intramuscularly daily for 8 weeks and three times weekly thereafter. The primary tumor was localized in the foregut (n = 11), midgut (n = 7), hindgut (n = 1), and unknown site (n = 3). Most cases had liver metastasis. Seventeen patients had elevated 5-hydroxyindoloacetic acid (5-HIAA) excretion and 5 had flushing and/or diarrhea as the only clinical manifestation. Six cases presented a complete syndrome (flushing, diarrhea and 5-HIAA excretion). Control of symptoms was obtained in 80% and a 5-HIAA level reduction in 58% of the patients. The interferon treatment was more effective for control of the carcinoid syndrome than for control of tumor growth. The treatment was well tolerated and fever, myalgia, anorexia and fatigue were the most frequent side-effects.

Recovery of response to adriamycin and cyclophosphamide by lonidamine in previously treated metastatic breast-cancer patients.

Thirty-one patients with metastatic breast cancer not responding or progressing after initial response to adriamycin + cyclophosphamide (AC) treatment entered a phase 11 study with oral lonidamine in association to AC. Objective clinical responses were observed in 10 patients (32%) and consisted of 1 complete + 9 partial remissions. Disease stability and progression were observed in 8 and 13 cases, respectively. These results were obtained with a marginal toxicity in addition to that already reported for AC therapy, the main additional side effect being myalgia, which was easily manageable in most cases.

Hodgkin's Disease in 50 Intravenous Drug Users with HIV-Infection.

Fifty cases of Hodgkin's disease in intravenous drug users (IVDU) have been collected by the Italian Cooperative Group on AIDS-Related Tumors (G.I.C.A.T.). Ninety-two per cent of the patients were males; the median age was 26 years. Persistent generalized lymphadenopathy (PGL) at onset was present in 54% of patients, AIDS in 9%, ARC in 9% while 28% were simply HIV-positive. The initial median absolute number of CD4 lymphocytes was 264/mmc. Opportunistic infections were diagnosed in 20% of patients. In most patients the histological pattern was that of mixed cellularity and lymphocytic depletion (76%). In almost half the initial symptom was a persistent lymph node enlargement due to PGL. In the majority of patients (58%) only a clinical staging and bone marrow biopsy could be performed due to the presence of opportunistic infections, rapid disease progression or refusal of pathologic staging procedures. One patient presented with a Waldeyer's ring involvement, but no other unusual presentations were observed. After MOPP alternated or followed by ABVD or MOPP alone, 15/29 CR (52%) and 14/29 PR (48%) were observed. The median duration of CR was 14 months, while the median survival of CR has not been reached; the median survival of patients treated with chemotherapy with CD4 values at presentation {geq}400/mmc was significantly superior to that in those with CD4 < 400/mmc. The overall median survival was 16 months. Twenty-eight per cent of patients receiving chemotherapy + radiotherapy developed opportunistic as well as non-opportunistic infections (21%). Lethal hepatic toxicity was observed in 2 patients. In conclusion, Hodgkin's disease in IVDU was not found to be associated with unusual presentations, as previously reported for homosexuals. Complete remissions could be achieved in over 50% of patients, but in IVDU non-opportunistic infections in addition to opportunistic infections may also limit treatment administration. The presence of parenchymal functional impairment due to drug abuse, or drug abuse-related infections, such as pneumonia, endocarditis and hepatitis, should lead to the choice of antitumour agents with no or only minor potential liver, lung and cardiac toxicity.

Chemotherapy versus tamoxifen versus chemotherapy plus tamoxifen in node-positive, estrogen receptor-positive breast cancer patients: results of a multicentric Italian study. Breast Cancer Adjuvant Chemo-Hormone Therapy Cooperative Group.

Between November 1, 1983 and June 30, 1987, 510 node-positive, estrogen receptor (ER)-positive breast cancer patients have been randomly allocated to receive either chemotherapy (six intravenous [IV] cyclophosphamide, methotrexate, and fluorouracil [CMF] courses followed by four IV epirubicin courses) or 5 years of tamoxifen treatment or a combination of both therapies. After a median follow-up of 40 months, patients receiving the combined treatment achieved the best results, and those treated with chemotherapy alone achieved the worst, the difference being particularly evident in postmenopausal women. However, while the concurrent use of chemotherapy and tamoxifen did improve the results achieved by chemotherapy alone, particularly in postmenopausal women and in those with four or more involved nodes, it did not significantly improve the results achieved by tamoxifen alone, particularly in patients with higher ER tumor concentrations. Side effects were more numerous and more severe in patients receiving chemotherapy (with or without tamoxifen). Our findings, although still preliminary, confirm that tamoxifen should be the treatment of choice for postmenopausal breast cancer patients with node-positive, ER-positive tumors. In addition, the findings suggest that tamoxifen may represent a safe alternative to chemotherapy (at least to the cytotoxic regimen we used) for younger women, provided they have ER-positive tumors. In patients with ER-positive tumors, the addition of chemotherapy to tamoxifen does not seem to improve significantly the effectiveness of tamoxifen alone.