Elf regimen in advanced gastrointestinal malignancies - an analysis of its clinical effectiveness and toxicity.

A multi-institutional phase 11 study of the combination of levofolinic acid 100 mg/m2, VP16 120 mg/m2 and 5-fluorouracil 500 mg/m2 for 3 consecutive days was carried out on a series of 73 evaluable patients with low performance status affected by locally advanced and/or metastatic gastrointestinal carcinomas. Site of primary tumor were: stomach 26, large bowel 20, pancreas 16, gall-bladder 5, and liver 6. Among patients with gastric carcinoma, 2 patients (8%) had a complete response with a mean duration of 6.8+ months, and 9 (35%) had a partial response with a mean duration of 5.8+ months, for an overall response rate of 43%. Overall response rate was largely unsatisfactory in colorectal carcinoma (20%), pancreatic (12%), gall-bladder and liver carcinomas. The treatment was very well tolerated with no grade 4 toxicity over a total of 267 cycles administered. Grade 3 leukopenia was seen in 25% of cases, and grade 2 thrombocytopenia in 18%. Vomiting never exceeded grade 2. Thus, the ELF regimen is quite active in advanced gastric carcinoma, and may be recommended as palliative treatment of patients who cannot receive intensive chemotherapy. On the other hand, it cannot be considered active in colorectal, pancreatic, gall-bladder and liver carcinomas, and its use should be discouraged in these neoplasms.

Single agent vinorelbine in the treatment of unresectable lung metastases from colorectal cancer.

Vinorelbine (VNR; 5'-nor-anydro-vinblastine) is a new semisynthetic vinca alkaloid which has demonstrated significant clinical activity against non-small cell lung cancer, bronchial adenocarcinoma, breast cancer, and head/neck squamous cell carcinoma. Moreover, vinorelbine has been widely employed in combination with cisplatinum with or without 5-fluorouracil for the treatment of lung cancer and head/neck carcinomas. Sixteen consecutive patients with lung metastases from colorectal adenocarcinomas were treated with vinorelbine tartrate (Navelbine R) given at the dose of 25 mg/m(2) i.v. bolus every week for eight consecutive times employing metoclopramide as an antiemetic tool. All patients had previous surgery, two had adjuvant chemo-immunotherapy with i.v. 5-fluorouracil and oral levamisole, 5 patients had adjuvant radiotherapy, and 1 patient had chemotherapy with levofolinic acid and 5-fluorouracil for advanced disease. Sites of disease included lung in all cases, liver metastases in 3 patients and nodal tumoral deposits in 2 cases. All patients entered in the study had lung disease as predominant site of disease and showed multiple metastases. One patient was not evaluable for response, toxicity and survival because he was lost to follow-up before completion of therapy. No major objective response was seen. Four patients had stable disease which lasted a mean of 5.2 months, and the remaining 11 patients showed progressive disease. Mean survival was 6.7+ months (range 4.0-12.0+ months). The treatment was quite well tolerated by most patients, granulocytopenia being the most frequent side-effect. Nausea/vomiting was very mild with grade 1 episodes in 5 patients (33%). Grade 1 leukopenia was seen in 5 patients (33%), grade 2 leukopenia in 3 patients (20%), and grade 3 in 2 cases (13%). Grade 1 thrombocytopenia was recorded in 3 cases (20%). No significant neurotoxicity was observed, except mild constipation in 4 cases (26%). The activity of VNR on a weekly schedule against lung metastases from large bowel adenocarcinoma is very low, however it should be noted that the treatment was well tolerated by most patients.

Cisplatin plus vp16 as salvage treatment for advanced breast-carcinoma resistant or recurrent after 1st line chemotherapy for metastatic disease.

Forty patients with chemotherapy refractory metastatic breast carcinoma were enrolled in a phase II study of cisplatin 80 mg/m2 on day 1 plus VP16 100 mg/m2 on days 1-3 every 28 days. The overall response rate was 32% (95% CL 17-47%), with 2 patients (5%) showing a CR with a mean duration of 11.3 months, and 11 patients (27%) a PR with a mean duration of 7.8+ months. Seven patients (17%) had stable disease, and 20 patients (50%) progressed despite chemotherapy. One complete response and 4 partial responses were obtained in patients previously untreated with antracyclines. The overall survival was 10.2+ months. The mean survival of responding patients (CR+PR) was 15.5+ months, while that of non responders (NC+PD) was 8.6+ months. A total of 188 cycles were administered (4.7 cycles/patient) and the most frequent toxicities were gastrointestinal and hematological side-effects. The most severe toxicities were intense vomiting and anemia. Grade 3 vomiting was seen in 11 patients (27%), and grade 1-2 anemia in 30% of cases. Severe grade 3 leukopenia was seen in only 12% of cases. Mild renal toxicity was recorded only in 2 cases, while alopecia was observed in almost all patients. In conclusion, although CDDP plus VP16 regimen, may be safely given on an outpatient basis, its routine use as salvage treatment for chemotherapy refractory metastatic breast carcinoma is not recommended. This regimen may, however, be employed as second line chemotherapy in selected cases.

Usefulness of oral medroxyprogesterone acetate in the management of cancer-related cachexia-anorexia syndrome.

A study on the activity and tolerability of high-dose medroxyprogesterone acetate in the treatment of ACS in neoplastic patients was carried out in a series of 103 patients with advanced cancer beyond cure with standard chemotherapeutic or radiotherapeutic treatments. The treatment plan was: medroxyprogesterone acetate (MAP) 1,000 mg/day as liquid suspension orally at a single dose, for at least one month. If there was no improvement in body weight, SSA, performance status therapy was interrupted. An increase in body weight greater than or equal to 5%, in SSA score greater than or equal to 2 points, in performance status and then in quality of life were recorded as positive MAP-related events. Therapy-related toxicity was evaluated according to the WHO criteria. A mean body weight increased from 63 kg recorded before therapy to 67 kg recorded after 30 days of MAP. This difference was statistically significant (p<0.001). SSA increased from baseline value of 2.4 to 4.7, and mean performance status from 58.4 to 65. Again, these difference were highly significant (p<0.005 and p<0.001 respectively). The improvement in both mean body weight and SSA were statistically significant independent of performance status. Data presented in the present study confirm the clinical effectiveness of oral medroxy-progesterone acetate in the management of anorexia-cachexia syndrome in patients with advanced cancer resistant to systemic chemotherapy.

Second line chemotherapy for metastatic colorectal carcinoma.

25 patients with metastatic colorectal carcinoma previously treated with 5-fluorouracil and folinic acid for advanced disease, were treated with mitomycin C 8 mg/m(2) i.v. bolus on day 1, adriamycin 40 mg/m(2) i.v. bolus on day 1, and lonidamine 150 mg per os t.i.d. starting one day before chemotherapy and stopping 2 days after the end of chemotherapy. Treatment was repeated every 4 weeks. All patients had previous surgery and systemic chemotherapy with 5-fluorouracil and folinic acid given as first line chemotherapy for metastatic tumor. Sites of disease included liver, lung, nodes, abdomen, and bone. All enrolled patients were evaluable for objective response. Only one patient, affected by rectal carcinoma, showed a partial response (4%) which lasted 5.8+ months. No complete response was seen. Stable disease was recorded in 4 cases (16%) with a mean duration of 4.6+ months. All remaining patients had progressive disease. Median overall survival was 8.7+ months. Toxicity was significant. Grade 3 thrombocytopenia was seen in 8 cases (32%), and grade 3 leukopenia in 5 cases (20%). Grade 3 vomiting was observed in 9 patients (36%). The combination of mitomycin C, adriamycin and lonidamine is not effective in the treatment of metastatic colorectal adenocarcinoma resistant to 5-fluorouracil-based chemotherapy. These data suggest that lonidamine is not able to potentiate antineoplastic activity of chemotherapeutic drugs in humans and its use in colorectal cancer should be avoided since it has no or little impact on response rate and survival.

A prospective randomized trial of thymopentin versus granulocyte--colony stimulating factor with or without thymopentin in the prevention of febrile episodes in cancer patients undergoing highly cytotoxic chemotherapy.

One hundred patients with advanced carcinoma undergoing highly cytotoxic chemotherapy were enrolled in a prospective randomized trial comparing subcutaneous G-CSF, thymopentin, a combination of the two, and placebo as preventive treatment of febrile leukopenia. Data from this study show that G-CSF was very active in reducing the incidence of chemotherapy-related fever and leukopenia as compared to placebo (22% versus 64%). This difference was statistically highly significant (P < 0.001). Thymopentin was associated with a reduction in febrile episodes as compared to placebo (52% versus 64%), but this difference did not reach statistical significance. Moreover, the addition of thymopentin to G-CSF did not result in a statistically significant improvement of results obtained with G-CSF alone. Similar results were achieved for fungal infections. Tolerance to thymopentin was excellent, while less than 9% of patients on G-CSF treatment complained of mild nausea and generalized bone pain.

Vinorelbine plus cisplatinum for the treatment of stage IIIB and IV non small cell lung carcinoma.

Thirty consecutive patients with stage IIIB-IV non small cell lung cancer were treated with a combination of cisplatin 80 mg/m2 on day 1 plus vinorelbine 25-30 mg/m2 on days 1, 8. This cycle was repeated every 3 weeks. The overall response rate was 46%, with 1 patient showing a complete response and 13 patients (43%) a partial response with a mean duration of 8.4+ months. Six patients had a stabilization and 10 progressed. The main toxicities were represented by myelosuppression and nausea/vomiting. Grade 3 leukopenia was seen in 33% of cases, grade 2 thrombocytopenia in 12%, and phlebitis in the injection vein in 16%. Mild constipation was also recorded. The combination of cisplatin plus vinorelbine is quite effective in advanced non small cell carcinoma of the lung, and may be safely given on an outpatient basis.

Intracavitary treatment of malignant pleural and peritoneal effusions in cancer patients.

Authors present a review of the intracavitary treatment of malignant effusions in cancer patients, experience with tetracycline, mechloretamine, quinacrine, radio-isotopes, interferon beta and interferon alpha are reviewed. Personal experience with interferon alpha is reported.

Vinorelbine plus cisplatin in recurrent or previously untreated unresectable squamous cell carcinoma of the head and neck.

Despite considerable progress achieved in the management of head and neck carcinomas (HNC) in the last decade, the prognosis of patients with advanced squamous cell HNC is still dismal. On the basis of the reported good activity of a new vinca alkaloid derivative, i.e., vinorelbine (VNR), we tested the combination of cisplatin and VNR in a series of patients with recurrent or previously untreated unresectable squamous cell HNC. Thirty-five patients with recurrent or previously untreated unresectable squamous cell HNC were treated with a combination of cisplatin 80 mg/m2 on day 1, plus vinorelbine 25 mg/m2 i.v. push on days 1 and 8. This cycle was repeated every 3 weeks. Analysis of response rates was carried out separately for previously untreated patients, and those with recurrent disease after surgery and/or radiotherapy. In the group of 20 patients with recurrent disease the overall response rate was 55% (95% CL 44-66%), with 3 patients (15%) showing a complete response with a mean duration of 6.2+ months and 8 patients showing a partial response with a mean duration of 8.6+ months. In the group of patients with previously untreated unresectable disease, 13 patients (87%, 95% CL 78-96%) had a major objective response with a complete response rate of 27%. This regimen was quite well tolerated, with meyelosuppression and vomiting being the most frequent toxicities. The occurrence of an acute pain syndrome following vinorelbine administration in 4 patients is noteworthy. In conclusion, this combination is active in advanced squamous cell head and neck carcinoma. However, although it may be recommended in recurrent carcinoma, the complete response rate achieved in previously untreated patients is lower than that reported with other more intensive regimens.

A prospective evaluation of the activity of human granulocyte-colony stimulating factor on the prevention of chemotherapy-related neutropenia in patients with advanced carcinoma.

After informed consent, 86 patients with advanced cancer undergoing potentially myelosuppressive cytotoxic chemotherapy were randomized to receive placebo or subcutaneous granulocyte-colony stimulating factor (G-CSF) 5 micrograms/Kg/day in order to prevent severe neutropenia and its related morbidity. The incidence of neutropenia (absolute neutrophil count < 1,000/mm3) was significantly reduced in patients receiving G-CSF than in controls (18% versus 42%; P < 0.05). The duration of neutropenia was also shortened by the administration of G-CSF (4.8 versus 8.2 days; P < 0.05). Therapy with G-CSF has also a positive impact on the dose-intensity of employed regimens. Patients treated with G-CSF showed oral fungal disease in 9% of cases, while control patients had a 21% incidence (NS). Patients treated with G-CSF received 91% of the programmed dose-intensity as compared to 71% of control patients (P < 0.05). These data strengthen the clinical usefulness of G-CSF in the prevention of chemotherapy-related neutropenia, infections, and reduction in dose-intensity. Further studies are required to establish if the increase in dose-intensity allowed by G-CSF treatment may positively influence the outcome of cancer patients.

Combination chemotherapy of 5-fluorouracil, epidoxorubicin and mitomycin C in the palliative treatment of locally advanced and/or metastatic adenocarcinoma of the stomach.

Thirty-seven consecutive patients with advanced and/or metastatic gastric adenocarcinoma received a combination of 5-fluorouracil 600 mg/m2 on days 1, 8, 29, 36; epidoxorubicin 75 mg/m2 i.v. on days 1, 29; mitomycin C 10 mg/m2 i.v. on day 1. This cycle was repeated every 8 weeks. Out of a total of 34 evaluable patients, 2 (5.8%) had a complete response and 7 (20.6%) had a partial response with an overall median duration of 40 weeks (range 20-128). The median survival of responding patients was not reached after a mean follow-up of 76 weeks, while that of patients with no change and progressive disease was reached at 36 and 13 weeks respectively. Treatment was generally well tolerated with hematological and gastrointestinal toxicities being the major side-effects. Despite the use of epidoxorubicin 75 mg/m2, the 26.4% (95% confidence limits 16-36%) objective response rate is not satisfactory. Evaluation of more aggressive protocols is strongly recommended within the limits of controlled trials.

Pharmacological modulation of 5-fluorouracil and its clinical implications: an overview.

Authors present an overview of the present knowledge in the field of biochemical modulation of 5-fluorouracil and its potential clinical applications. Interaction between 5-fluorouracil and several modulators, such as leucovorin, interferons, cisplatin, hydroxyurea, thymidine, methotrexate, and PALA are extensively analyzed.

[Our experience in the use of somatostatin in upper digestive hemorrhages]. / La nostra esperienza sull'uso della somatostatina nelle emorragie digestive alte.

The paper illustrates the Authors' personal experience of the use of somatostatin in high digestive hemorrhages. Endoscopy continues to be the principal method for hemorrhage diagnosis and therapy and the additional use of somatostatin undoubtedly accelerates recovery by blocking gastric and pancreatic secretions and blood flow at the splanchnic level.

[Observations in sclerosing cholangitis]. / Alcune osservazioni sulla colangite sclerosante.

Sclerosing cholangitis is a rare liver disease of unknown etiology with a slow but progressive course. The authors report their experience and illustrate some surgical procedures to preserve bile duct patency in view of a liver transplantation program.

Programmable, very low noise current source.

We propose a new approach for the realization of very low noise programmable current sources mainly intended for application in the field of low frequency noise measurements. The design is based on a low noise Junction Field Effect Transistor (JFET) acting as a high impedance current source and programmability is obtained by resorting to a low noise, programmable floating voltage source that allows to set the sourced current at the desired value. The floating voltage source is obtained by exploiting the properties of a standard photovoltaic MOSFET driver. Proper filtering and a control network employing super-capacitors allow to reduce the low frequency output noise to that due to the low noise JFET down to frequencies as low as 100 mHz while allowing, at the same time, to set the desired current by means of a standard DA converter with an accuracy better than 1%. A prototype of the system capable of supplying currents from a few hundreds of µA up to a few mA demonstrates the effectiveness of the approach we propose. When delivering a DC current of about 2 mA, the power spectral density of the current fluctuations at the output is found to be less than 25 pA/√Hz at 100 mHz and less than 6 pA/√Hz for f > 1 Hz, resulting in an RMS noise in the bandwidth from 0.1 to 10 Hz of less than 14 pA.

An extraordinary testimonial of thermal rehabilitation: Giuseppe Garibaldi - 2011: 150th Anniversary of the Italian Unification.

On the occasion of the 150th Anniversary of the Italian Unification, the discovery of some letters by Giuseppe Garibaldi - referring to a period of thermal treatments at the Baths in Civitavecchia (Rome) - gave us the opportunity for writing a commentary about a not well known experience in the Two World Hero's life: the numerous treatments carried out at many Italian spa centres for treating a rheumatic pathology (probably a rheumatoid polyarthritis) and the outcomes of various war wounds, especially the famous gunshot-wound in his right ankle during the Battle of Aspromonte, in 1862.