Pemetrexed in combination with oxaliplatin as a first-line therapy for advanced gastric cancer: a multi-institutional phase II study.

BACKGROUND: This clinical trial assessed the efficacy of pemetrexed combined with oxaliplatin (PEMOX) in patients with advanced gastric cancer (AGC). PATIENTS AND METHODS: Forty-four patients with untreated AGC were enrolled to evaluate response rate (RR). Patients received pemetrexed (500 mg/m(2)) with vitamin supplementation and oxaliplatin (120 mg/m(2)) every 21 days for six cycles or until disease progression occurred. RESULTS: Median age was 62 years (range 26-76). The majority of patients (93%) had metastatic disease. Sixteen of the 44 patients achieved confirmed response [RR 36%; 95% confidence interval (CI) 22% to 52%]; four complete responses and 12 partial responses (complete and partial responses according to the RECIST guidelines are the confirmed-responses observed in the study population). Median time to tumor progression (TTP) was 6.2 months (95% CI 4.3-7.5) and median survival was 10.8 months (95% CI 7.7-17.2). A total of 220 cycles were administered, with a median of six cycles. Most common grade 3/4 toxic effects were neutropenia in 41% of patients (19% of cycles) and thrombocytopenia in 11% of patients (4% of cycles). Treatment delays or dose reductions for toxicity occurred in 10% and 5% of cycles, respectively. CONCLUSIONS: PEMOX is active and well tolerated in AGC. RR, TTP, and survival were comparable to those achieved in studies using different 5-fluorouracil (5-FU)-oxaliplatin combinations, without the inconvenience of prolonged 5-FU schedules.

Mediastinal large-B-cell lymphoma with sclerosis: a clinical study of 21 patients.

We report the clinical findings of 21 consecutive patients affected by mediastinal large B-cell lymphoma with sclerosis. This type of lymphoma is a recently described histopathologic entity characterized on clinical grounds by distinctive features, which, according to our series, can be summarized as follows: young age (median, 30 years; range, 15 to 42 years), prevalence of females over males (15 v six), rare occurrence of superficial lymph node enlargement (three of 21 patients), and involvement of unusual extranodal sites (kidney six, adrenal cortex two patients). The clinical course appears to be closely related to treatment. In fact, complete remission (CR) was not obtained in the six patients submitted to conventional cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP plus bleomycin (CHOP-Bleo) regimens until 1985, as opposed to 13 CRs reached in the 15 patients subsequently treated with more aggressive regimens after 1985 (methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin [MACOP-B], 12 patients; methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone [M-BACOD], two patients; and vincristine, cyclophosphamide, fluorouracil, cytarabine, doxorubicin, methotrexate, and prednisone [F-MACHOP], one patient; plus involved-field radiotherapy, 10 patients). Among the 13 patients who achieved a CR, only one relapse was observed at 10 months. The median overall survival of complete responders after an observation period of 11 to 69 months has not yet been reached, and the event-free survival curve indicates that 90% of patients who achieve CR may be potentially cured.

Cytofluorimetric evaluation of DNA ploidy in lung cancer: a bronchoscopic study.

The study of the biological characteristics of lung cancer is gaining more and more interest both because of their potential role as prognostic indicators and for therapeutic reasons. The DNA content estimated by flow cytometry in surgical samples of non-small cell lung cancer (NSCLC) has already been demonstrated to be correlated with survival in these patients. From July 1990 to February 1992 we analyzed the DNA distribution of bronchoscopic biopsies from 88 patients with lung cancer (18 small cell lung cancer, SCLC, and 68 NSCLC, two unspecified histology). Twenty-eight tumors (34.6%) had a diploid DNA distribution, while 53 were aneuploid (65.4%). A correlation was found between DNA ploidy and survival. Evaluation of the DNA content in bronchoscopic samples in a large series of patients could determine the role of this analysis prior to surgery in NSCLC and its value as a marker with respect to prognosis and response to therapy in SCLC.

Inductively coupled plasma mass spectroscopy quantitation of platinum-DNA adducts in peripheral blood leukocytes of patients receiving cisplatin- or carboplatin-based chemotherapy.

Platinum-DNA adducts can be assayed in peripheral blood leukocytes by means of atomic absorption spectroscopy and ELISA, and high adduct levels have been correlated previously with favorable clinical response to platinum-based chemotherapy. Our purpose was to study adduct formation in peripheral blood leukocytes by means of a new method, inductively coupled plasma mass spectroscopy (ICP-MS), and to correlate adduct formation with clinical response and toxicity. Platinum (Pt)-DNA adducts were measured by means of ICP-MS in leukocytes of 66 patients receiving a cisplatin- or carboplatin-based chemotherapy, collected either before the beginning of treatment and incubated in vitro with cisplatin or 1 and 24 h after the administration of drug to the patient. The Pt-DNA adduct level in leukocytes from patients exposed to drug in vitro was 14.33 +/- 14.71 fmol/microgram DNA (mean +/- SD), which was not significantly different from the value of 23.4 +/- 19.53 fmol/microgram DNA observed in leukocytes from nine healthy volunteers. In samples collected after the administration of chemotherapy, Pt-DNA adducts ranged from 1.91 +/- 3.59 fmol/microgram DNA (mean +/- SD) at the 1-h time point to 2.61 +/- 3.35 fmol/microgram DNA at 24 h (P > 0.05). Adduct levels in leukocytes exposed in vitro did not correlate with adduct levels from patients treated with cisplatin-based chemotherapy (r = 0.085 and 0.011 at 1 and 24 h, respectively). At 24 h, adduct levels in patients receiving cisplatin (3.15 +/- 3.64 fmol/microgram DNA, mean +/- SD) were significantly higher (P = 0.02) than those observed in patients treated with standard dose carboplatin (0.57 +/- 0.73 fmol/microgram DNA) and also higher than those in patients receiving high-dose carboplatin (1.18 +/- 1.06 fmol/microgram DNA), although the latter difference did not reach statistical significance (P = 0.071). No differences in adduct levels (mean +/- SD) were evident between patients responsive (3.23 +/- 3.51 fmol/microgram DNA) and nonresponsive (2.34 +/- 3.01 fmol/microgram DNA) to chemotherapy. In the homogeneous group of patients treated with combination of cisplatin and 5FU, received dose intensity, hemoglobin decrease, and posttreatment creatinine could not be linked with the extent of leukocyte adduct formation. The data presented here demonstrate that ICP-MS allows the detection of adducts in patients treated with cisplatin or carboplatin and suggest that adduct formation in leukocytes is not a major determinant of response or toxicity.

bcl-2 but not p53 expression is associated with resistance to chemotherapy in advanced breast cancer.

Programmed cell death is an important determinant of the response to chemotherapy. Among the factors controlling this process, a significant role is played by bcl-2 and p53, the expression of which, together with estrogen receptor content and tumor proliferative activity, was investigated by means of immunohistochemistry in 55 advanced breast cancer patients (median age, 60 years; range, 25-71 years). Analysis of bcl-2 expression identified two groups of patients with a significant difference in response rate. A total of 17 patients (31%) responded to chemotherapy (5 had a complete response and 12 had a partial response): 14 of 32 (44%) bcl-2-negative patients (< 40% stained cells) and only 3 of 23 (13%) bcl-2-positive patients (> or = 40% of stained cells; P = 0.019 by Fisher's exact test). The two groups were well balanced in terms of age, performance status, disease-free survival, menopausal status, and type of chemotherapy. bcl-2-negative tumors showed a tendency toward a higher p53 expression and proliferation rate, whereas an excess of bone as the dominant disease site was evident among the bcl-2-positive ones. However, the only variable to result significantly different between the two groups was estrogen receptor expression (P = 0.004). A multivariate logistic regression model showed that bcl-2 maintained its power of discriminating two groups with a different probability of responding to chemotherapy, although the greatest contribution was given by dominant disease site and type of chemotherapy. In conclusion, the results of this study suggest a possible role for bcl-2 in predicting resistance to chemotherapy.

Gamma knife radiosurgery in brain metastases from testicular tumors.

To our knowledge, there are no published reports on the effectiveness of radiosurgery in the management of brain metastases from testicular nonseminomatous germ cell tumor. The authors evaluate the results of gamma knife (GK) treatment in three patients with these unusual intracranial lesions. Between April 1995 and July 2001, three patients with brain metastasis from testicular nonseminomatous germ cell tumor underwent adjuvant radiosurgery at our department. The primary tumor had been surgically removed in all cases. At diagnosis, one patient was stage IB and two were stage III poor risk. Chemotherapy and whole brain radiotherapy were administered before radiosurgery in all cases. Pre-GK radiotherapy was administered with a daily fraction dosage of 1.8-2.0 Gy. The indications for radiosurgery were tumor volume <20 cm3, microsurgery too risky, refusal of surgery. All the lesions were located in eloquent brain areas. Post-GK high-dose chemotherapy with autologous peripheral-blood stem-cell rescue was administered in two cases due to systemic recurrence of the disease. All patients are still alive with a median and mean follow-up period after radiosurgery of 63 and 68.3 mo, respectively. They had no neurological deficits at the latest examination. Neuroradiological follow-up invariably showed tumor growth control (complete response in two cases and partial response in one) with typically delayed post-radiosurgical imaging changes (transient in two cases and long-lasting in one). In conclusion, GK seems to be highly effective and safe in brain metastases from testicular nonseminomatous germ cell tumor. In cases with diffuse metastatic brain involvement, the whole brain radiotherapy preceding radiosurgery should be delivered with 1.8 Gy daily fraction to prevent the risk of long-lasting post-radiosurgical imaging changes.

Teniposide as single drug therapy for elderly patients affected by small cell lung cancer.

From January 1987 to December 1990, 26/105 previously untreated patients affected by small cell lung cancer (SCLC), not suitable for intensive SCLC treatment since 19 of them were older than 70 years and 7 suffered from severe chronic diseases, received induction therapy consisting of teniposide alone, 60 mg/m2 on days 1-5, every 3 weeks until disease progression. After a minimum of two courses, 24 patients were evaluable for response: 13 with limited disease (LD) and 11 with extensive disease (ED) (2 patients were unevaluable: 1 early death and 1 protocol violation). Response rate, by disease stage, was: in the 13 LD, 1 complete response (CR), 8 partial responses (PR), 2 minor responses and 2 failures; in the 11 ED, 1 CR, 4 PR and 6 failures. The overall response rate was 58% (14/24) (95% confidence limits = 38-78%), comprising 8% CR and 50% PR. Median duration of response was 7 months (range 2-32). Median overall duration of survival was 9 months (range 1.5-36+). Toxicity was haematological WHO grade III in 13% of courses delivered, whereas no further important side-effects were recorded, excluding alopecia, which was common. Teniposide used alone appeared a safe and effective palliative treatment for poor-risk patients; the major limitation was the low CR rate.

Postoperative chemotherapy increases the disease-free survival rate in primary gastric lymphomas stage IE and IIE.

We describe 53 patients with primary gastric non-Hodgkin's lymphoma (38 stage IE,15 stage IIE) treated with surgery as a primary procedure. According to the Working Formulation, 13 cases had low, 21 had intermediate and 19 had high grade malignancy. 34 patients considered at high risk received postoperative polychemotherapy. The overall 10-year disease-related survival is 91%. Median follow-up is 52 months. 7 patients relapsed (13%). The 10-year disease-free survival rate of the 19 patients initially treated with surgery is 60%, as compared with 92% in the patients who also received chemotherapy (P = 0.004). However, overall survival did not differ between the two groups, since two-thirds of the patients who relapsed after surgery alone were rescued with chemotherapy. Stage, age, sex and histology did not correlate with survival. In our experience, surgery was an adequate first step procedure; the addition of chemotherapy significantly reduced relapses and increased the disease-free survival rate in patients with unfavourable prognostic factors.

Alpha-interferon activated cytotoxic lymphocytes in hairy cell leukemia patients: evaluation of cytotoxic events.

To further define the mechanisms responsible for the alpha-interferon (alpha-IFN) efficacy in the treatment of hairy cell leukemia (HCL), experiments were carried out to specify the cytotoxic events taking place following this type of therapy. Although an increased natural killer (NK) activity was demonstrable after alpha-IFN treatment, evidence has been provided that hairy cells were not specifically lysed either by fresh autologous/allogenic NK lymphocytes or by lymphokine activated killer (LAK) cells. This property could not be induced in vitro by alpha-IFN or by interleukin-2 (IL-2). Our data favour the hypothesis that the increase of NK cell activity observed following alpha-IFN therapy has not a direct antineoplastic effect but is likely to be of relevance for a non-specific enhancement of the host immune system. In alpha-IFN treated HCL this latter property may account for the better resistance to infections which usually represents the major cause of mortality in these patients.

Primary extranodal lymphomas of Waldeyer's ring, stage IE and IIE.

We reviewed 45 cases of Waldeyer's ring lymphomas (25 stage IE, 20 IIE): 73% had high-grade histology according to Kiel's classification. Fourteen patients received radiotherapy alone and 31 chemotherapy, combined with radiotherapy in 28. Complete remission rate was 95% and relapse rate 32%. At 8 years overall disease-related survival (DRS) and event-free survival (EFS) were 69% and 57% respectively. Combined treatment provided both significantly better DRS (82% vs 42%) and EFS (76% vs 25%) than radiotherapy alone. Most of the patients with high-grade histology (26/33) received the combined treatment and this subgroup achieved a long-term EFS of 78%. Both DRS and EFS were also significantly longer in patients under 60. At multivariate analysis favorable prognostic factors were lower age for DRS and combined treatment for EFS.

A phase II study of induction chemotherapy with gemcitabine (G) and cisplatin (P) in locally advanced non-small cell lung cancer: interim analysis.

BACKGROUND: Gemcitabine-cisplatin (GP) combination is one of the most active and well tolerated regimens in advanced non-small cell lung cancer (NSCLC). The aim of this study is to evaluate the activity and toxicity of the GP regimen as a 21-day schedule in patients (pts) with stage IIIAN2-IIIB NSCLC. PATIENTS AND METHODS: From October 1997 to July 2000, 47 pts entered the study: 43 were eligible (40 men and three women); median age was 61 years (range 45-73); ECOG PS 0-1; histology was squamous (20 pts), adenocarcinoma (12 pts), large cell (five pts), and undifferentiated (six pts); stage was IIIAN2 (14 pts, 32.56%), and IIIB (29 pts, 67.44%). Malignant pleural effusion or superior vena cava syndrome was criteria of exclusion. Induction treatment consisted of three cycles of GP (G 1250 mg/m(2) i.v. on days 1 and 8, and P 100 mg/m(2) on day 8 every 3 weeks). Responding and stable pts underwent surgery (S) and/or radiotherapy (RT). RESULTS: Following a minimum of two cycles, 39 pts were evaluable for response and 42 for toxicity. Two pts had complete responses (CR; 5.2%), 24 had partial response (PR; 61.5%), eight had stable disease (SD; 20.5%), and five had progressive disease (PRO; 12.8%). WHO grades 3 and 4 anaemia, neutropenia and thrombocytopenia were observed in two, four and two pts, respectively; non-haematological toxicity was moderate. After induction, stable and responding pts received either RT (18 pts) or S+RT (13 pts). Among the 16 resected pts, a radical complete resection was possible in 13 cases (81.3%), whereas tumour down-staging was observed in nine pts (56.2%). CONCLUSION: GP, as a 3-week neoadjuvant schedule, appears a safe and active regimen.

Cisplatin versus carboplatin in combination with mitomycin and vinblastine in advanced non small cell lung cancer. A multicenter, randomized phase III trial.

BACKGROUND: In advanced not selected NSCLC chemotherapy achieved an advantage of approximately 1-2 months on median survival versus best supportive care. Chemotherapy seems to improve symptoms control, even if randomised studies with quality of life as first endpoint are lacking and often chemotherapy toxicity compromises the frail cost/benefit ratio. The aim of the present study is to evaluate the impact on QoL, substituting cisplatin, a pivot drug in NSCLC therapy, with carboplatin, an analogue with an improved toxicity profile. The combination of cisplatin with Mitomycin and Vinblastine was one of the most frequently used in the palliative setting at the time of design of our study. METHODS: Patients were randomized to receive MVP regimen (Mitomycin-C 8 mg/m2 d1, Vinblastine 4 mg/m2 d 1-8, Cisplatin 100 mg/m2 d1) or MVC regimen (Mitomycin-C 8 mg/m2 d1, Vinblastine 4 mg/m2 d 1-8, Carboplatin 300 mg/m2 d1) every 3 weeks. The QoL was evaluated by the Spitzer QL-Index and by the EORTC QLQ-C30+LC 13 questionnaires before chemotherapy, after one cycle, after three cycles, and then every 6 weeks in the first 6 months and every 3 months thenafter. RESULTS: From September 1994 to July 1997, 153 consecutive patients were randomized to MVP (75 patients) or MVC arm (78 patients). Despite difficulties in carrying out and analysing QoL items in such patients, the global QoL evaluated by the Spitzer's questionnaire suggested an advantage for MVC regimen (P=0.05) and a significant difference was observed in global health subdomain (P=0.04). The disease-related symptoms improved with time, and the benefits lasted for the entire treatment period. When evaluated with the EORTC questionnaire there was significantly less nausea and vomiting (P=0.0001), appetite loss (P=0.01), insomnia (P=0.03), constipation (P=0.01) and peripheral neuropathy (P=0.01) in favour of MVC, and a trend for less hair loss (P=0.05). The advantage lasted for all the duration of chemotherapy. No differences were observed in global quality of life subdomain (P=0.40) between the two regimen. QoL was the first endpoint and the statistical power was inadequate to assess other parameters. However, we reported a response rate of 43.1 and 38.6%, respectively, in MVP and MVC arm (P=0.59) and a median survival of 10.2 and 7.2 months, respectively, for cisplatin and carboplatin arm (P=0.39). CONCLUSIONS: The carboplatin containing regimen (MVC) has a significant better toxicity profile than the cisplatin containing (MVP) regimen as proven both by the EORTC questionnaires and by the WHO toxicity data reported by physicians. No significant differences in terms of response rate, time to progression and overall survival were observed between the two regimen. The two chemotherapy regimen showed a similar effectiveness in symptom palliation when evaluated with C30 addendum of EORTC QOL questionnaire. With the Spitzer's questionnaires a trend towards an improved quality of life index was observed during treatment with the carboplatin combination in comparison to the cisplatin combination. This difference, however, was not observed when the global quality of life was evaluated with the EORTC patients compiled questionnaires. A carboplatin containing regimen with better toxicity profile and a similar potentiality for symptoms control offers an option in comparison to similar cisplatin containing combinations in the palliative treatment of advanced NSCLC.

Pseudomonas septicaemia. A review of 60 cases observed in a university hospital.

Epidemiological, clinical features and the pathogenesis of 60 cases of pseudomonas septicaemia, observed over a period of 7 years from 1975 to 1981, are described. The mean frequency of occurrence was 0.40 episodes per 1000 admissions and an incidence of 66 per cent was observed in patients with serious underlying diseases, such as haematological malignancies and neoplasia. Thirty-seven patients had received cytotoxic and immunosuppressive therapy and showed a marked leukopenia, and whenever the leukocyte count fell below 2000/mm3, the prognosis was significantly worse. The most common portals of entry were the respiratory and gastrointestinal tracts. The overall mortality was very high (75 per cent) and mainly related to septic shock. Apart from the very high frequency of this complication (24 patients, 40 per cent of all cases), a typical clinical picture, distinguishing pseudomonas from other Gram-negative septicaemias, did not emerge.

Phase II randomized study of dacarbazine, carmustine, cisplatin and tamoxifen versus dacarbazine alone in advanced melanoma patients.

This randomized phase II trial was performed to define the activity and toxicity of the combination of dacarbazine (DTIC), carmustine (BCNU), cisplatin (DDP) and tamoxifen (DBDT regimen) versus DTIC alone in patients with metastatic melanoma. Sixty patients with metastatic melanoma were randomly assigned to receive BCNU 150 mg/m2 intravenously (i.v.) on day 1, cisplatin 25 mg/m2 i.v. daily on days 1 to 3, DTIC 220 mg/m2 i.v. daily on days 1 to 3 and tamoxifen 160 mg orally daily for 7 days prior to chemotherapy (DBDT arm; arm A). Treatment cycles were repeated every 28 days, while BCNU was given every two cycles. The DTIC arm (arm B) patients received DTIC alone 1200 mg/m2 i.v. on day 1, repeated every 21 days. Patients were evaluated every two cycles; responding patients continued the treatment for a maximum of 12 cycles. The overall response rate was 26% in the DBDT arm and 5% in the DTIC arm. Complete responses were 2.5% for DBDT and 0% for DTIC. The median progression-free survival and the median survival were 4 and 9 months, respectively for DBDT, and 2 and 7 months for DTIC. DBDT was associated with significant haematological toxicity: 33% of the patients experienced a grade III or IV neutropenia and 28% a grade III or IV thrombocytopenia. In conclusion, the overall response rate obtained with DBDT was greater than that obtained with DTIC alone; however, this combination increases toxicity with limited impact on overall survival.

Oral ondansetron (GR38032F) for the control of acute and delayed cyclophosphamide-induced emesis.

The efficacy of the serotonin antagonist ondansetron (GR38032F, Glaxo) was evaluated in the prevention of nausea and vomiting induced by combinations containing cyclophosphamide (CTX) greater than or equal to 600 mg/m2 IV day. At their first treatment course, 55 patients (10 males, 45 females) median age 55 years (range 31-76) were given ondansetron 8 mg orally tds for a minimum of 3 to a maximum of 5 days. 54 patients were evaluable. Complete and major control of acute (day 1) emesis was observed in 94.5% of patients and acute nausea was graded as absent or mild in 83.3% of cases. Complete and major control of emesis improved on subsequent study days from 96.1% on study day 2 to 100% on study day 5. Side effects were mild. Ondansetron is a safe and effective antiemetic drug.

Small cell lung cancer (SCLC): a randomized trial of cyclophosphamide, adriamycin, vincristine plus etoposide (CAV-E) or teniposide (CAV-T) as induction treatment, followed in complete responders by alpha-interferon or no treatment, as maintenance therapy.

In this phase III, double-random study, we compared CAV-E to CAV-T combination as induction treatment (1st randomization) for SCLC. Subsequently, patients achieving a complete response (CR) were randomized again (2nd randomization) to receive maintenance treatment with alpha-IFN or no treatment. From June 1990 to June 1992, 75 untreated patients were enrolled in this trial. After stratification according to limited disease (LD) or extensive disease (ED), patients were randomized to receive the following treatment: cyclophosphamide 1000 mg/m2, adriamycin 50 mg/m2, vincristine 2 mg, day 1 i.v., plus etoposide (E) 100 mg/m2 (CAV-E: arm-A) or teniposide (T) 60 mg/m2 on day 2, 3, 4 i.v., every 3 weeks (CAV-T: arm-B). LD patients after 3 cycles of treatment received chest radiotherapy and 2 further cycles, whereas ED patients received 5 consecutive cycles. Patients who achieved a CR entered the 2nd randomization receiving a-IFN (3 x 10(6) I.U., i.m. daily x 9 months) or no treatment. A second-line treatment with carboplatin 300 mg/m2 plus E (if T was initially used) or T (if E was initially used) was also scheduled for patients achieving less than CR to induction treatment. Preliminary results are as follows: 75 patients were randomized, 72 were eligible for survival (arm-A = 37 and arm-B = 35) and 60 were fully evaluable for response (arm-A = 34 and arm-B = 26). In patients with LD the overall response rate was 79% (CR 21%) in arm-A vs 92% (CR 50%) in arm-B. In patients with ED, the overall response rate was 80% (CR 33%) in arm-A vs 84% (CR 7%) in arm-B. At a mean observation time of about 1 year (range 1-25 months), median survival of LD patients was 15 months in arm-A and 13 months in arm-B (Chi-square = 1.55; p > 0.05); in ED patients survival was 10.8 months and 8 months respectively (Chi-square = 2.88; p > 0.05). Cumulative survival probability was identical (12 months) in all patients of both arms. Toxicity was mainly haematologic and gastrointestinal: WHO grade 3-4 myelosuppression and vomiting were observed in 20% and 11% respectively, of cycles delivered in arm-A, compared to 19% and 8%, respectively, of cycles in arm-B. Two septic deaths occurred with CAV-T, while 1 patient discontinued treatment due to persistent myelosuppression with CAV-E. After the first and second-line treatment 20 patients showed a CR.(ABSTRACT TRUNCATED AT 400 WORDS)

Extragonadal germ cell tumor: a clinical study.

Among 18 patients with primary extragonadal germ cell tumors (8 seminoma and 10 non- seminoma), the disease involved the mediastinum (7), the retroperitoneum (8), multiple lymph nodal sites (2) and the pinealis gland (1). Seventeen patients received cisplatin-based chemotherapy as part of the initial treatment. Fifteen patients (83%) achieved complete remission (6 seminoma and 9 non-seminoma): 12 of them are relapse-free after a median follow-up of 82 months (range 13-138). Five-year overall survival was 65%. No statistically significant survival difference was found between mediastinal and retroperitoneal tumors or patients with seminoma and nonseminoma.

Combination of chemotherapy and radiotherapy improves the cure rate in primary extranodal lymphomas of the head and neck (PLHN).

BACKGROUND: Since PLHN are rare, prognostic factors and the therapeutic strategy have not yet been clearly assessed. PATIENTS AND METHODS: Seventy-one patients with PLHN (44 stage I, 27 stage II; 54 with high-grade histology) received the following treatments: 5 radical surgery, 21 radiotherapy, 43 combined treatment (mainly chemotherapy plus radiotherapy) [CT] and 1 was not treated. RESULTS: Disease-related survival (DRS) and disease-free survival (DFS) were 84% and 69% at 5 years and 70% and 56% at 10 years. CT provided significantly better DRS and DFS than radiotherapy alone (92% and 81% vs 70% and 43% respectively), though the group receiving the CT included most of the patients with high-grade histology (37) and stage II (20). Outcome was not influenced by stage and site of involvement (Waldeyer's ring vs non-Waldeyer's ring). Multivariate analysis showed that favourable prognostic factors were age for DRS, high-grade histology and CT for DFS. CONCLUSIONS: Patients receiving the CT fared significantly better, though most of them had high-grade histology and stage II.

Gemcitabine and continuous infusion of 5-fluorouracil in locally advanced and metastatic pancreatic cancer: a phase I-II study.

BACKGROUND: Gemcitabine has been recently recognized as standard treatment in advanced pancreatic cancer. To potentiate its single-agent activity we conducted a phase I-II study with the primary objective of establishing the maximum tolererated dose (MTD) of gemcitabine and continuous infusion 5-FU in patients with locally advanced or metastatic pancreatic cancer. PATIENTS AND METHODS: Fifteen patients received a fired dose of 5-FU 200 mg/mq protracted infusion for six months. Gemcitabine was administered weekly for three out of four weeks for six cycles at escalating doses of 800 mg/mq to 1100 mg/mq. RESULTS: MTD was established at 1000 mg/mq of gem citabine. Of the 11 evaluable patients, 7 patients had stable disease, 1 had partial response and 3 had progressive disease. Of the 14 patients evaluable at follow-up, median time to progression was 5 months. Median survival was 10 months. CONCLUSION: This study confirms the good tolerability of the combination, of gemcitabine with 5-FU.