Oral sucrosomial iron versus intravenous iron in anemic cancer patients without iron deficiency receiving darbepoetin alfa: a pilot study.

PURPOSE: Erythropoiesis-stimulating agents (ESAs) are often used in treatment of patients with chemotherapy-induced anemia. Many studies have demonstrated an improved hemoglobin (Hb) response when ESA is combined with intravenous iron supplementation and a higher effectiveness of intravenous iron over traditional oral iron formulations. A new formulation of oral sucrosomial iron featuring an increased bioavailability compared to traditional oral formulations has recently become available and could provide a valid alternative to those by intravenous (IV) route. Our study evaluated the performance of sucrosomial iron versus intravenous iron in increasing hemoglobin in anemic cancer patients receiving chemotherapy and darbepoetin alfa, as well as safety, need of transfusion, and quality of life (QoL). MATERIALS AND METHODS: The present study considered a cohort of 64 patients with chemotherapy-related anemia (Hb >8 g/dL <10 g/dL) and no absolute or functional iron deficiency, scheduled to receive chemotherapy and darbepoetin. All patients received darbepoetin alfa 500 mcg once every 3 weeks and were randomly assigned to receive 8 weeks of IV ferric gluconate 125 mg weekly or oral sucrosomial iron 30 mg daily. The primary endpoint was to demonstrate the performance of oral sucrosomial iron in improving Hb response, compared to intravenous iron. The Hb response was defined as the Hb increase ≥2 g/dL from baseline or the attainment Hb ≥ 12 g/dL. RESULTS: There was no difference in the Hb response rate between the two treatment arms. Seventy one percent of patients treated with IV iron achieved an erythropoietic response, compared to 70% of patients treated with oral iron. By conventional criteria, this difference is considered to be not statistically significant. There were also no differences in the proportion of patients requiring red blood cell transfusions and changes in QoL. Sucrosomial oral iron was better tolerated. CONCLUSION: In cancer patients with chemotherapy-related anemia receiving darbepoetin alfa, sucrosomial oral iron provides similar increase in Hb levels and Hb response, with higher tolerability without the risks or side effects of IV iron.

Real-world experience of abiraterone acetate plus prednisone in chemotherapy-naive patients with metastatic castration-resistant prostate cancer: long-term results of the prospective ABItude study.

BACKGROUND: Limited real-world data exist on the effectiveness and safety of abiraterone acetate plus prednisone (abiraterone hereafter) in the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) naive to chemotherapy. Most of the few available studies had a retrospective design and included a small number of patients. In the interim analysis of the ABItude study, abiraterone showed good clinical effectiveness and safety profile in the chemotherapy-naive setting over a median follow-up of 18 months. PATIENTS AND METHODS: We evaluated clinical and patient-reported outcomes (PROs) of chemotherapy-naive mCRPC patients treated with abiraterone as for clinical practice in the Italian, observational, prospective, multicentric ABItude study. mCRPC patients were enrolled at abiraterone start (February 2016-June 2017) and followed up for 3 years; clinical endpoints and PROs, including quality of life (QoL) and pain, were prospectively collected. Kaplan-Meier curves were estimated. RESULTS: Of the 481 patients enrolled, 454 were assessable for final study analyses. At abiraterone start, the median age was 77 years, with 58.6% elderly patients and 69% having at least one comorbidity (57.5% cardiovascular diseases). Visceral metastases were present in 8.4% of patients. Over a median follow-up of 24.8 months, median progression-free survival (any progression reported by the investigators), time to abiraterone discontinuation, and overall survival were, respectively, 17.3 months [95% confidence interval (CI) 14.1-19.4 months], 16.0 months (95% CI 13.1-18.2 months), and 37.3 months (95% CI 36.5 months-not estimable); 64.2% of patients achieved ≥50% reduction in prostate-specific antigen. QoL assessed by Functional Assessment of Cancer Therapy-Prostate, the European Quality of Life 5 Dimensions 3 Level, and European Quality of Life Visual Analog Scale remained stable during treatment. Median time to pain progression according to Brief Pain Inventory data was 31.1 months (95% CI 24.8 months-not estimable). Sixty-two patients (13.1%) had at least one adverse drug reaction (ADR) and 8 (1.7%) one serious ADR. CONCLUSION: With longer follow-up, abiraterone therapy remains safe, well tolerated, and active in a large unselected population.

FOLFOX-4 regimen as fist-line chemotherapy in elderly patients with advanced gastric cancer: a safety study.

Gastric cancer is often diagnosed in advanced stage (AGC) and in elderly patients. Current chemotherapies induce severe toxicity and are difficult to deliver. Some authors have shown the activity and safety of oxaliplatin with various 5-fluorouracil (FU) and leucovorin (LV) infusions in AGC. The aim of our study was to evaluate the feasibility of the FOLFOX-4 regimen in elderly patients with AGC. From 6/2003 to 7/2005, 33 patients (median age 74 years, range 66-79 years) were enrolled into the study. 31 patients were assessable for the safety analysis and for response. We recorded complete response in 4 patients (13%), partial response in 6 patients (19%), 9 (29%) stable disease and 12 progressive disease for an overall response rate of 32% (95% CI, 16% to 48%). At median follow-up of 20 months the median time to progression was 6.4 months. The therapy was well tolerated, the main G1/2 toxicities were nausea, vomiting and diarrhea. Only 2 patients suffered from severe vomiting. Severe hematologic toxicities were uncommon. Anemia G3 was recorded in 3 patients, neutropenia G3 in 6 patients and febrile neutropenia in 1 patient. G1 and G2 neurotoxicity were a common event while G3 sensorial neuropathy was not reported. We conclude that although our patients were elderly and most had a PS 2, the regimen was manageable, easy to deliver, well accepted by the patients and active.

A modified weekly docetaxel schedule as first-line chemotherapy in elderly metastatic breast cancer: a safety study.

Standard dose docetaxel is burdened by severe toxicity. Weekly schedules have been shown to be active as standard scheme with reduced side effects. In 20-30% of elderly patients (pts) the classic 6-week schedule induces grade 3/4 fatigue and other cumulative toxicities. We carried out this safety study in order to evaluate whether a modified weekly docetaxel schedule would improve the toxicity profile. Twenty-one untreated elderly (> or = 70 years) pts suffering from metastatic breast cancer were enrolled in the study. Pts were treated with a weekly dose of 35 mg/m2 docetaxel for 6 weeks, followed by a 2-week rest. Further cycles were performed with this modified schedule: docetaxel days 1, 8 and 15 every 29 days. All pts received at least the first cycle (6 weeks). A total of 261 doses were delivered. No toxic deaths occurred. The toxicity was mild: we recorded 1 episode of grade 3 neutropenia and severe asthenia in only 2 pts (10%). We recorded an overall response rate of 33% (1 CR, 6 PR). Our data showed a reduced incidence of severe asthenia (2/21), obtained with a light modification of a weekly docetaxel schedule.

Novel therapeutic approaches to cancer patients with bone metastasis.

Bone metastases are a common event in advanced cancer. Breast, lung, prostate and thyroid neoplasms have striking osteotropism. Bone metastatic cancer may be associated with catastrophic consequences for the patients. Therefore, new strategies are warranted in order to reduce the incidence of bone metastases and to palliative established skeletal disease. External beam radiation therapy, endocrine treatments, chemotherapy, bisphosphonates and radioisotopes are all important. Bisphosphonates have become the treatment of choice for tumor-induced hypercalcaemia and more recently they have been used alone or in combination with cytotoxic agents in the palliative treatment of patients with bone metastases. The results are encouraging. Currently, new bisphosphonates that are a hundred times more powerful with respect to clodronate and pamidronate are under investigation. The treatment of metastases to bone and mechanisms of pain relief after radiation therapy are poorly understood. Up to date, there are not standard criteria for the irradiation of bone metastases and bone pain relief may be reached using a variety of fractionation schemes. Radionuclide therapy is the systemic use of radioisotopes for bone pain. It is currently regarded as suitable for comparison with wide-field irradiation, but appears to have major disadvantages in terms of pain relief and toxicity.

External radiation therapy boost to the vaginal vault: feasibility of intracavitary dosimetry using a commercial diode system.

PURPOSE: An overall check of the whole dosimetry procedure by intracavitary in vivo dosimetry, using n-type silicon diode dosimeter, was performed during 6-MV x-ray irradiation of the vaginal vault. The dose delivered to the isocenter by all treatment fields was evaluated. METHODS AND MATERIALS: The diode dosimeter was calibrated against an ion chamber and tissue maximum ratio, field size factor, SSD factor, and temperature dependence studies were performed. Diode system accuracy, linearity, and reproducibility were also tested. Patients' dose data were collected and comparision was made with respect to treatment-planning dose calculations. Ten patients with cervical cancer and endometrial cancer were treated with surgery and irradiation. During the boost to the vaginal vault, a diode was inserted by an intravaginal device and the vaginal vault was the isocenter of the four fields. The field size generally was not larger than 10 x 10 cm2. RESULTS: Diode-measured "tissue maximum ratio" agreed to within 1% with those measured with an ion chamber in field from 7 x 7 to 10 x 10 cm2. The diode also exhibited a temperature dependence of 0.1% degrees C(-1). For 10 patients treated with a 6-MV beam, the agreement with treatment-planning dose calculations was shown to be better than +/-4%. CONCLUSION: The good accuracy and reproducibility of the diode system shows that determination of the dose at isocenter, for patients treated in the pelvic region, can be performed with n-type diodes accurately. On the other hand, in the vaginal vault boost, external-beam radiotherapy is delivered accurately and in vivo dosimetry is really not indicated.

Telomere length maintenance in aging and carcinogenesis.

Normal somatic cells have a finite number of divisions, a limited capacity to proliferate. Human telomeres, the long DNA TTAGGG repeats at the ends of chromosomes, are considered a molecular clock marker. The gradual and progressive telomere shortening at each replicative cycle is associated, through the activation of pRB and p53 pathways and genomic instability, to the replicative senescence, a non-dividing state and widespread cell death. Activation of telomere maintenance [telomerase; or alternative lengthening of telomeres mechanisms (ALT), or other adaptive responses] can revert this program. Although not completely known, several mechanisms and modulating agents may be able to up and down-regulate telomere length and its maintenance. Chemopreventive therapies for the up-regulation of telomerase activity, able to prolong the life of cell cultures in a phenotypically youthful state, could have important applications in research and medicine. On the contrary the therapeutic down-regulation of telomerase activity may be used in cancer therapy. Telomerase expression per se is not oncogenic, but telomere shortening and maintenance seem to be crucial events in tumor formation. Thus a particular focus has been pointed out relatively to the immortalization of normal or potential pre-cancerous cells. With the extension of life span the probability to get in contact with carcinogens increases, genetic instability, oncogene activation and/or onco-suppressor gene inactivation (i.e. p53, pRB, ras): the cancer transformation can be then induced in predisposed cells, depending on their genetic context, by the activation of telomere maintenance. Pharmacological intervention may be able to modulate the rate of living, by increasing life span of few specific target cells, or decreasing it in proliferating . Because of the unknown state of the enormous cell number of the human organism, is it safe to extend the human life span by therapeutic agents?

Curative radiotherapy (RT) using limited RT treatment fields in elderly patients with non-small cell lung cancer in clinical stage IIIA.

We report a prospective phase II study utilizing limited radiotherapy (RT) treatment fields in elderly (greater than or equal to 75 years) patients (pts) with non-small cell lung cancer (NSCLC) in clinical stage IIIA. Sixteen good risk pts with histologically confirmed NSCLC in clinical stage IIIA, age greater than or equal to 75 years (yr) (range 75-83; median age 77) were entered in the study. All pts were treated with Limited RT fields (including T and N1-2 usually with a 1.5 cm, radiographic margin) and received a minimum of 54 Gy (range 54-62 Gy, median 60 Gy, dose/fraction 2 Gy/5 dd a week). All pts have been followed-up for a median time of 3.5 years (range 1.75-6.58). Median survival (MS) was 18 months (range 7-52 months). No acute and/or late significant toxicity was recorded. Univariate analysis showed a better survival in pts receiving a radiation dose greater than or equal to 60 Gy, with an MS of 34 vs 14 months (p=0.017) and in pts with Karnofsky Performance Status greater than or equal to 80, with an MS of 34 vs 12 months (p=0.0O2). There are scarce data available on survival in elderly pts with NSCLC in clinical stage IIIA. Pts submitted to 'standard' RT in unresectable NSCLC have a poor median survival time and 5-year survival rates. The results obtained in our pts encourage us to use 'limited' RT in elderly but the results require a phase III study before definitive recommendations can be made.

Escalating dose of oral ondansetron in the prevention of radiation induced emesis.

BACKGROUND: Radiation-induced emesis is an event linked to the release of serotonin during abdominal irradiation. Ondansetron is able to prevent emesis, but an optimal scheme has not yet been established. The aim of our study was to evaluate the efficacy of an escalating dose of oral ondansetron (Oral OND) in the prevention of emesis induced by fractionated radiotherapy. PATIENTS AND METHODS: We enrolled 30 patients who underwent fractionated radiotherapy involving the upper abdomen which received this schedule of antiemetic therapy: phase A Oral OND 4 mg p.o. immediately after irradiation (RT) with a dose < or = 20 Gy; phase B Oral OND 8 mg p.o. immediately after RT with dose > 20 Gy and < 30 Gy; phase C Oral OND 8 mg p.o. every 12 hours starting immediately after RT with a dose > or = 30 Gy. RESULTS: During phase A we obtained a 100% of CR in all 30 patients. In phase B 22 CR (92%) and 2 MR (8%). In phase C on a total of 11 patients we recorded 6 CR (55%), 3 MR (27%) and 2 F (18%). The toxicity was mild. CONCLUSION: Our data confirm the efficacy and safety of Oral OND and, moreover, show the possibility to reduce the cost without compromising the activity.

Gemcitabine as single agent in the treatment of elderly patients with advanced non small cell lung cancer.

BACKGROUND: In phase II trials gemicitabine proved to be an active agent in NSCLC, producing a clinical benefit, often higher than response rate. PATIENTS AND METHODS: We assessed the impact of gemcitabine treatment on response rate and quality of life in 21 untreated elderly patients (aged > 70 years) with NSCLC. Gemcitabine (1250 mg/sm) was administered days 1-8 every 21 days. Response and toxicity were analyzed according to WHO criteria. The assessment of quality of life was performed by analysing a disease symptom related questionnaire completed by the patient. RESULTS: All the patients were evaluable: we found 7 PR (33%), 5 SD (24%) and 9 PD; the median duration of response was 24 weeks; the median overall survival 32 weeks; WHO grade 2 leukopenia (in 4 patients) and thrombocytopenia (grade 3 in 1 patient and grade 2 in two patients) were the main toxic effects. A clinical benefit was demonstrated in all 12 patients with PR or SD and in 3 patients with PD. CONCLUSIONS: These data confirm that gemcitabine is a well tolerated and active therapeutic approach in elderly non small cell lung cancer patients.

Efficacy of two oral dose regimens of granisetron.

BACKGROUND: Most chemotherapic treatments are carried out on an outpatient basis. In such patients the prevention and control of emesis is important. Granisetron is a specific and extremely potent 5-HT3 antagonist available as an oral formulation. We have carried out an open randomized crossover study in patients receiving moderately emetogenic chemotherapy. MATERIALS AND METHODS: 30 patients were randomized to receive one of the two oral dose regimens of GRAN. Treatment A = 1 mg of GRAN initially and 12 hours after the first; treatment B = a single 2 mg dose of GRAN. RESULTS. An overall good response for vomiting was reached in 70% and 86.7% respectively of patients receiving treatments A and B (p = 0.0625). Good response to nausea was reached in 73.3% of the patients with treatment A and in 76.7% with treatment B (p = 1). 68.3% of patients did not record chemoinduced emesis. CONCLUSION: We believe that oral GRAN alone is an active and safe drug for the prevention of acute chemoinduced emesis.

Defibrotide in the prevention of venous irritation by vinorelbine administration.

BACKGROUND: Vinorelbine is active in a variety of malignancies. The most common side effects are leukopenia and granulocytopenia, moreover Vinorelbine is a vescicant and venous irritant, the incidence of the latter being 10-26% in patients who received VNB as a 20-30 minute peripheral infusion. To prevent venous toxicity we have carried out a study in order to evaluate the efficacy of Defibrotide in this issue. MATERIALS AND METHODS: 41 patients were enrolled in the study, the experimental schedule was: Defibrotide 400 mg on 250 cc of normal saline iv, after 15 minutes of infusion, we delivered quick, brief and repeated pulses of Vinorelbine through the plastic tube followed by remaining Defibrotide: For grading venous irritation we used the scale by Rittenberg et al. RESULTS: A total of 360 infusion were delivered, the incidence of any venous irritation was 5% and maximum grade 2. No severe toxicity was recorded. CONCLUSION: These data show that Defibrotide might serve as a therapeutic drug to prevent vascular toxicity by Vinorelbine.

Primitive sinonasal malignant mucosal melanoma: description of a case treated with radiotherapy (0-7-21 regimen).

Mucosal malignant melanoma (MMM) of the nasal cavity and paranasal sinuses is rare and has a poor prognosis. The rarity of MMM of the ethmoid is also noteworthy and primary treatment has been, till now, surgery and/or radiotherapy (RT). Here we report a case of MMM arising in the ethmoid of a caucasian man and treated with hypofractionated RT. A 32 year-old man presented with symptoms of cephalalgia, obstruction and nasal bleeding; a computed tomography (CT) showed a large mass that involved ethmoid, left orbit and roof of the nasal cavity. After biopsy, a MMM was found. Chest radiography demonstrated the presence of multiple lung metastases and still the patient was submitted to palliative radiotherapy according to 0-7-21 regimen with a total dose of 24Gy/3 fraction/21dd, dose per fraction 8Gy. The patient was asymptomatic one month after the end of RT and three months later a CT demonstrated a partial remission. The patient died 17 months after the initiation of RT for disseminated disease, without clinical signs of tumoral regrowth in the irradiated site. This case confirms the efficacy and the safety of 0-7-21 RT regimen; the absence of symptoms after 17 months and the poor prognosis encourage the use of RT as primary treatment for MMM of the head and neck.

Complete regression of primary gastric MALT-lymphoma after double eradication Helicobacter pylori therapy: role and importance of endoscopic ultrasonography.

The authors report on a case of complete regression of primary gastric Mucosa Associated Lymphoid Tissue MALT-lymphoma after double eradication Helicobacter pylori therapy. They analyze the diagnostic role of endoscopic ultrasonography and the therapeutic aspects, on the grounds of literature data and personal experience are analyzed.

Supraclavicular lymph node metastases (SLM) from breast cancer as only site of distant disease: has radiotherapy any role?

BACKGROUND: Supraclavicular lymph node metastases (SLM) as the only site of metastatic disease from breast cancer is a rare and a poor prognostic event. In order to evaluate the role of Radiotherapy (RT) with "radical dose" to the supraclavicular fossa, we carried out a non randomized clinical trial comparing systemic therapy alone to integrated and aggressive treatment (systemic therapy plus radiotherapy). The primary end-point was time to progression (TTP). The second end-point was the overall survival (OS). METHODS: From 1/1/1989 to 31/12/1994 37 patients (with or without the presence of locoregional disease) were enrolled into two arms, of the study, but were allowed, when giving their consent, to change the arm of the study which they had been originally allotted to. Arm A, 18 patients, 15 evaluable: chemo +/- hormonotherapy for 6 courses; after the second course, if local progression disease was present, the pts. were submitted to RT and removed from the study (3 patients). Arm B, 19 patients all evaluable: chemo +/- hormonotherapy for 3 courses followed by RT with "radical" dose. Results were analyzed on 30/11/1995 and no interim analysis was performed. The potential median follow up for all patients was 56.5 months (range 11-83 months): for Arm A 61 months (range: 12-82); for Arm B 53 months (range: 11-83). The two groups were homogeneous and balanced, without statistical differences. RESULTS: Median TTP was 12.5 months in Arm A and 19.5 months in Arm B (p = 0.064). Median overall survival (OS) was 27.5 months in Arm A and 48 months in Arm B. T-status to the time of the diagnosis was found to be independent prognostic factor for TTP (p = 0.0029). Disease-free interval from diagnosis to recurrence was found to be a significant prognostic factor for OS (p = 0.009). CONCLUSION: The results in Arm B demonstrated the opportunity of a long term control in this subset of patients. Therefore we suggest the start of a wider multicenter study in order to define the biological significance of SLM, its importance in staging breast cancer and to consider the optimum treatment.

Prognostic factors in ambulatory patients with inoperable locoregionally recurrent rectal cancer following curative surgery.

BACKGROUND: The optimal treatment for locoregionally recurrent rectal cancer after curative surgery has not yet been defined. The definition of prognostic factors could lead to the selection of an aggressive therapeutic approach in patients with favourable prognosis alone. PATIENTS AND METHODS: The records of thirty-nine ambulatory pts, 15 female and 24 male, with diagnosis of locoregionally recurrent rectal cancer (LRRC) after curative surgery and treated with radiotherapy were retrospectively analyzed. The following factors were analyzed for their ability to predict the clinical response and outcome for LRRC: age, sex, initial tumor grading, primary surgical approach, initial primary tumor stage according to Dukes' classification, disease free survival (time to primary surgery and detection of a LRRC), pelvic-perineal structure affected by recurrence, total radiation dose, chemotherapy with fluorouracil, symptomatic response to the therapy, locoregional symptomatic re-recurrence, systemic progression disease. RESULTS: In the univariate analysis, predictive factors for survival, were graded (G1-2 vs G3 p = 0.04), Dukes' stage at first diagnosis (A-B vs C p = 0.01), and site of pelvic-perineal recurrence (Pelvic mass alone yes vs no p = 0.01; Nerve and/or Osseous involvement yes vs no p < 0.001). Following therapy for LRRC, a better survival was observed in pts with a complete symptomatic response (complete remission vs partial remission vs no change p < 0.001), without a further locoregional symptomatic re-recurrence (re-recurrence, yes vs no p = 0.001) and/or appearance of metastatic disease (yes vs no p < 0.001).

Ondansetron plus dexamethasone in the control of high dose cisplatin-induced emesis.

Twenty-two patients who underwent chemotherapy with cisplatin (CDDP) at doses > 100 mg/m2 also received antiemetic treatment comprised of the combination of ondansetron plus dexamethasone. The results obtained have shown a good activity from this combination with these high doses of CDDP, with a response of 81.8% (complete+major protection). There were also three therapeutic failures in patients with a few negative prognostic characteristics. It is our intention to use a benzodiazepine and adequate psychological support in an attempt to increase the response percentages in these kinds of patients.

Bleomycin, epirubicin, carboplatin (BECA) in the treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck.

The aim of this study was to evaluate three active agents, bleomycin (BLM), epirubicin and carboplatin in a new combination (BECA) in terms of feasibility, activity and toxicity in patients with recurrent and metastatic squamous cell carcinoma of the head and neck. From April 1992 to February 1993 15 pts (12M/3F), median age 53 years, all pretreated (6 surgery + radiotherapy; 3 radiotherapy + chemotherapy; 6 radiotherapy), were treated with BLM 15 mg/m2 days 1-14; epirubicin 30 mg/m2 days 1-14 and carboplatin 300 mg/m2 day 1 every 28 days. In the 14 evaluable pts we observed 1 complete response, CR (7.1%), 4 partial responses, PR (28.6%), 5 stable disease, SD and 4 disease progression, PD with an overall response of 35.7%. The treatment was globally well tolerated, 1 pt with grade 3 leukopenia and 1 pt with grade 3 thrombocytopenia, 1 pt with grade 3 emesis and 1 pt with grade 3 mucositis. At the last follow-up the duration of CR was 34 months, the duration of PRs were respectively 22-10-10-7 months, but the SD ranged from 4 to 6 months. The overall median survival was 8 months (3-36), 14 for responders and 4 for non-responders. This final report seems to confirm the activity and efficacy of the BECA regimen, suitable for outpatient administration with an overall response equal to other more aggressive combinations.

Concurrent carboplatin and radiotherapy in the treatment of squamous cell carcinoma of the head and neck, stage IV. Preliminary data of a phase II study.

About two-thirds of the patients with squamous cell carcinoma of the head and neck (SCCHN) are diagnosed when the disease is in a locoregionally advanced stage. If surgery is not advisable, radiotherapy is the only treatment presently available to obtain radicality. In order to improve the therapeutic efficacy of radiotherapy (RT), chemotherapy has been associated with it with the aim of eradicating possible micrometastatic foci outside the radiotherapic fields and to enhance the cytotoxic effects of radiation. Results with concomitant chemoradiotherapy have been encouraging. We carried out a phase II study with the combination of carboplatin 300 mg/m2 every 21 days and RT at conventional doses in SCCHN stage IV (non M1). We obtained an overall response of 85.7% with an 18-month survival of 70%. The toxicity was moderate. These results encourage us to continue the accural of patients.

Etoposide, l-leucovorin and fluorouracil (ELF) regimen in metastatic gastric cancer: a phase II study.

The role of chemotherapy in metastatic gastric cancer (MGC) is predominantly palliative, therefore regimens with mild toxicity and acceptable activity should be preferred. The combination of etoposide, leucovorin and 5-fluorouracil (ELF) is suitable chemotherapy in this situation. We have enrolled 33 patients with MGC, using the following chemotherapy schedule: l-leucovorin 150 mg/m2 10 minute i.v., followed by etoposide 120 mg/m2 50 minute i.v., followed by 5-fluorouracil 500 mg/m2 10 minute i.v. on days 1-3, every 22 days. All patients are valuable for response, toxicity and survival. Two patients achieved complete response (6%), 10 patients (30%) had a partial response (PR), 9 patients (27%) had stabilization of disease (SD) and 12 patients had disease progression (PD). The median survival for all patients was 6 months (range, 1 to 40+). ELF was well tolerated, the main toxicity being myelosuppression. No toxic deaths occurred. In conclusion, the ELF regimen in our trial demonstrated, in this kind of patient, moderate activity in the absence of relevant toxicity, confirming its suitability in patients in generally poor condition.