Combined treatment with high-dose methotrexate, vincristine and procarbazine, without intrathecal chemotherapy, followed by consolidation radiotherapy for primary central nervous system lymphoma in immunocompetent patients.

OBJECTIVES: To assess the feasibility and the activity, as well as the efficacy to treat meninges, of chemotherapy (CHT) containing high-dose methotrexate (HD-MTX) followed by radiation therapy (RT), without intrathecal CHT, in patients with primary central nervous system lymphoma. METHODS: Eligibility criteria were histologically proven diagnosis, disease limited to the CNS, age < or = 70, ECOG performance status < or = 3, HIV-negative and no prior treatment. Thirteen patients (1996-1999; median age 54 years) received two courses of vincristine 1.4 mg/m2 day 1, MTX 3 g/m2 days 3 and 10 and procarbazine 100 mg/m2 days 1-14 every 4 weeks. Patients who achieved a complete remission were referred to RT, those with progressive disease were excluded from further study; all the remaining patients received a third course of CHT followed by RT. RESULTS: Twelve patients responded to CHT (overall response rate = 92%, complete response rate = 77%): 9 underwent consolidation RT, 3 did not. Two patients experienced severe acute toxicity; lethal pulmonary thromboembolism and transient renal failure. Five patients relapsed: 2 after CHT and 3 after RT. Relapse was local in all cases, with a case of concomitant hepatic involvement. No cases of ocular or meningeal relapse were observed. In contrast to high-dose cytarabine-containing CHT, salvage therapy with temozolomide produced good results. Two patients died of treatment-related neurotoxicity. Six patients are alive with a median follow-up of 17 months, and a 2-year overall survival (OS) of 61%. The median survival of the 9 patients who completed the planned treatment is 25+ months with a 2-year OS of 80%. CONCLUSIONS: HD-MTX, procarbazine and vincristine followed by RT, without intrathecal therapy, produce similar results with respect to other HD-MTX-containing regimens. These results seem to suggest that adequate meningeal treatment is possible without intrathecal drug delivery, even in CSF-positive patients. Corroborating data from a larger series are, however, necessary. Temozolomide should be tested in relapsed patients in a phase II prospective trial.

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.

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)

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.

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.

Cisplatin (P) versus cyclophosphamide, adriamycin and cisplatin (CAP) for stage III-IV epithelial ovarian carcinoma: a prospective randomized trial.

In 1982 a randomized trial was started to compare a cisplatin-containing polychemotherapy (CAP: cyclophosphamide - CPA 750 mg/m2, adriamycin - ADM 50 mg/m2, cisplatin - P 50 mg/m2 on day 1 every 21 days) with full-dose cisplatin as single agent (P 60 mg/m2/day on days 1 and 2 every 28 days) in 44 patients undergoing exploratory laparotomy or debulking surgery for stage III-IV epithelial ovarian carcinoma with residual disease greater than 5 cm. The response was evaluated at second-look surgery with random biopsies and peritoneal washing. On the basis of the final results the authors underline some data which, although merely indicative (because of the small number of patients) appear to be worth considering since they are in accordance with the latest reports: a) similar response rate (CR + PR = 47%) to first-line treatment in the two groups; b) the CAP treatment may achieve a longer median duration of CRs than the P treatment (20 versus 11 months); c) overall survival seems similar in the two groups of patients (19 versus 18 months), whereas the survival of CRs seems longer in the CAP treated patients (greater than 32 versus 25 months). The authors also discuss some observations on a possible salvage therapy.

Combination of mitomycin C + etoposide in advanced gastric carcinoma.

In June 1981 the authors activated a trial to evaluate the therapeutic effectiveness of the combination mitomycin C (MMC) + etoposide (VP 16) in previously untreated gastric carcinoma with measurable neoplastic lesions. Drugs were administered according to the following schedule: MMC, 12 mg/m2 i.v. day 1, + VP 16, 150-200 mg/m2 orally days 2, 3, 4, 22, 23, 24 every 6 weeks. The response rate (CR+PR) was 16.7%, which is not higher than that obtained when MMC and VP 16 are used as single agents. Overall median survival (8 months) was similar to that reported in the recent literature with combination chemotherapy.

[Experimental study on the use of cisplatin in oncology]. / Contributo sperimentale sull'impiego del Cisplatino in oncologia.

29 patients affected by ovarian (9 cases), head and neck, and miscellaneous neoplasms were treated with Cisplatinum. Most cases had been previously treated with different drugs. Complete and partial remission achieved significative results in 4, 7 and 9 ovarian patients. In the patients with head and neck tumor no complete remission and 4 partial remissions were obtained. These observations confirm that Cisplatinum may be a useful drug in chemotherapy of cancer.

Lithium carbonate in the treatment of drug-induced leukopenia in patients with solid tumors.

The authors report on the first part of an ongoing controlled trial (52 cases) on the evaluation of the effectiveness of Li2CO3 treatment of drug-induced leukopenia in patients with solid tumors. The results indicate that treatment with 750 mg/day per os of Li2CO3 for 7 days is capable of raising the leukocyte count to a highly significant extent, without serious side effects. The leukocytosis is due to an increase in neutrophil granulocytes.

Variations in serum copper and ceruloplasmin levels in advanced gastrointestinal cancer treated with polychemotherapy.

Serum copper and ceruloplasmin levels (SCL, SCeL) in 57 patients with advanced cancer of the stomach (35 cases) or large intestine (22 cases) treated with polychemotherapy were studies. In gastroenteric cancer, SCL, which are already high in untreated patients, have a tendency to increase further in cases of progression of the disease, while they seem to significantly decrease in cases of remission. SCeL during the trial appeared to be correlated to the clinical evolution of the disease only in the case of stomach cancer. In large intestine cancer, SCeL did not show any significant variation in relation to the normal range. These observations, in particular on the behavior of SCL in the neoplasms of the digestive tract, are in accordance with the results of other studies. The authors are inclined to attach a diagnostic and prognostic value to the variation in SCL and SCeL in gastrointestinal cancer.