Ambulatory high-dose methotrexate administration as central nervous system prophylaxis in patients with aggressive lymphoma.

High-dose methotrexate (HD-MTX) at 3 g/m2 is one of the strategies for central nervous system (CNS) prophylaxis in the first-line treatment of aggressive lymphomas, especially in diffuse large B cell lymphoma patients with high-risk CNS-International Prognostic Index. The objective of our study was to retrospectively analyze the safety of 2 cycles of systemic HD-MTX administered as an ambulatory regimen. Between January 2013 and December 2016, 103 patients were carefully selected on 6 criteria, including age < 60, albumin > 34, performance status 0 or 1, normal renal and hepatic functions, good understanding of practical medical guidance, and no loss of weight. Strict procedures of HD-MTX infusion were observed including alkalinization, urine pH monitoring, and leucovorin rescue. Renal and hepatic functions were monitored at days 2 and 7. MTX clearance was not monitored. Toxicities and grades of toxicity were collected according to the NCI-CTCAE (version 4.0). Among the 103 selected patients, 92 (89%) patients successfully completed the planned 2 cycles of HD-MTX on an outpatient basis. Eleven patients completed only 1 cycle, 3 because of lymphoma progression and 8 because of toxicity including 3 grade II hepatotoxicity, 2 grade I/II renal toxicity, 1 grade III neutropenia, 1 active herpetic infection, and 1 grade III ileus reflex. Reported adverse events (AE) included 92 (84%) grade I/II and 18 (16%) grade III/IV. Grade III hepatotoxicity, mostly cytolysis, was the most frequent AE observed with 8 (8%) events. Grade III/IV hematologic toxicities concerned 9 patients with 8 grade III/IV neutropenia and 1 thrombocytopenia. Renal toxicity was rare, mild, and transient, observed with 4 (4%) grade I/II events. Ambulatory administration of HD-MTX at 3 g/m2 without MTX clearance monitoring is safe with strict medical guidance. It requires careful selection of patients before administration, and a renal and hepatic monitoring after the administration.

Neoadjuvant transcatheter arterial chemoembolization and systemic chemotherapy for treatment of clear cell sarcoma of the kidney in children.

BACKGROUND: Clear cell sarcoma of the kidney (CCSK) is a rare and aggressive malignant renal tumor. We describe our experience with neoadjuvant transcatheter arterial chemoembolization (TACE) and systematic chemotherapy for the treatment of advanced CCSK in children. METHODS: Between January 2010 and December 2016, seven patients (3 boys and 4 girls; median 2.2 years) with advanced CCSK received preoperative TACE of renal artery and systemic chemotherapy. The chemoembolic emulsion for TACE consisted of cisplatin, pirarubicin, vindesine, and iodized oil. Preoperative systemic chemotherapy with vindesine, ifosfamide, and etoposide was administered three weeks after TACE. Nephrectomy was performed three weeks after systemic chemotherapy. After surgery, patients received radiotherapy and postoperative chemotherapy. RESULTS: No cardiotoxicity, renal insufficiency, or hepatic dysfunction was found in any patients. Grade II-III marrow suppression developed in four patients. One patient with tumor progress during neoadjuvant therapy failed to successfully undergo surgery and died. Six patients underwent nephrectomy after neoadjuvant therapy. Median follow-up period was 49.5 months (range, 11-83 months). Five patients have recurrence-free survival. One patient is still in postoperative chemotherapy after nephrectomy, radiotherapy and thoracoscopic resection of lung metastases. CONCLUSIONS: Neoadjuvant TACE and systemic chemotherapy appeared to be feasible in the treatment of advanced CCSK in this pilot study. THE TYPE OF STUDY: A case series with no comparison group. LEVEL OF EVIDENCE: Level IV.

Adjuvant chemotherapy versus surgery alone for esophageal squamous cell carcinoma: a meta-analysis of randomized controlled trials and nonrandomized studies.

The effect of adjuvant chemotherapy on survival of patients with thoracic esophageal squamous cell carcinomas is still controversial, and the subgroup of patients who will most likely benefit from the adjuvant chemotherapy on long-term survival has not yet been identified clearly. Studies published from 1995 to May 2012 were searched in Medline, Embase, PubMed, Cancerlit, the Cochrane Library, CNKI and major scientific meetings. Randomized controlled trials and nonrandomized studies comparing surgery plus adjuvant chemotherapy with surgery alone in patients with resectable thoracic esophageal squamous cell carcinomas were included. Eleven studies with a total of 2047 patients were identified, consisting of the adjuvant chemotherapy arm (n = 887) and surgery-alone arm (n = 1160). There was not statistically significant benefit on 3-year overall survival for adjuvant chemotherapy (risk ratio [RR] = 0.89, 95% confidence interval [CI], 0.72 to 1.09; P = 0.25). Adjuvant chemotherapy could significantly prolong the 1-year disease-free survival (DFS) (RR = 0.68, 95%CI, 0.51 to 0.89; P = 0.006), but not 3-year DFS (RR = 0.97, 95%CI, 0.73 to 1.29; P = 0.84). Further analysis showed that patients with stage III-IV diseases could benefit from adjuvant chemotherapy on 3-year overall survival (RR = 0.43, 95%CI, 0.31 to 0.61; P = 0.00001), but not in the case of patients with stageI-IIdiseases (RR = 1.12, 95%CI, 0.65 to 1.93; P = 0.68). Additionally, patients with positive lymph node could benefit on 5-year DFS from adjuvant chemotherapy (RR = 0.79, 95%CI, 0.64 to 0.99; P = 0.04). The modality treatment with adjuvant chemotherapy for patients with squamous cell carcinoma of thoracic esophagus might be determined according to pathological stage or the status of lymph node metastasis.

A retrospective study of the preoperative treatment of advanced Wilms tumor in children with chemotherapy versus transcatheter arterial chemoembolization alone or combined with short-term systemic chemotherapy.

PURPOSE: To evaluate the therapeutic effect of preoperative transcatheter arterial chemoembolization (TACE) combined with short-term systematic chemotherapy in the treatment of advanced Wilms tumor. MATERIALS AND METHODS: This was a retrospective study on 66 patients with unilateral advanced Wilms tumor, age 5 months to 11 years (median, 2.9 years; 30 boys and 36 girls), treated at our institution between 1995 and 2007. Characteristics of the patient population were maximal tumor diameter > 10 cm, or involvement of periaortic lymph nodes, or inferior vena cava invasion, or distal metastasis, or tumor with anaplastic histology. Patients were divided into three groups. Twenty patients were treated with conventional preoperative chemotherapy (PC group) using vindesine, actinomycin D, and pirarubicin for 4 weeks; 21 patients were treated in the TACE group with preoperative renal arterial chemoembolization using Lipiodol-pirarubicin-vindesine emulsion; and 25 patients were treated with preoperative chemoembolization combined with short-term systematic chemotherapy (T+S) for 2 weeks. RESULTS: No drug-induced cardiotoxicity, nephrotoxicity, or hepatic dysfunction was observed. Complete surgical removal of the tumor was achieved in 12 (65.0%), 17 (80.9%), and 22 (88.0%) patients in the PC, TACE, and T+S groups, respectively (T+S group vs PC group, P = .030). The 2-year relapse-free survival rates were 65.0%, 80.9%, and 100.0% in the PC, TACE, and T+S groups, respectively (T+S vs PC, P = .001). CONCLUSIONS: From our experience, preoperative chemoembolization combined with short-term systematic chemotherapy is able to achieve higher rates of complete tumor resection and relapse-free survival in the treatment of advanced Wilms tumor.

New insight into epirubicin cardiac toxicity: competing risks analysis of 1097 breast cancer patients.

BACKGROUND: Current recommendations that cancer patients receive a maximum cumulative dose of 900 mg/m(2) epirubicin are based on the risk of epirubicin-mediated cardiotoxicity and do not take into account the competing risk of death from cancer. Here, we identify risk factors for cardiotoxicity and overall mortality and determine the cumulative dose of epirubicin that yields a 5% risk for cardiotoxicity for cancer patients from different risk backgrounds. METHODS: Data were collected from 1097 consecutive anthracycline-naive patients treated for metastatic breast cancer with epirubicin. Patients who developed congestive heart failure classified as New York Heart Association class 2 or higher were recorded as having cardiotoxicity. Independent Cox multiple regression analyses for cardiotoxicity and for overall mortality were followed by competing risks analysis, with cardiotoxicity as the primary event and death from all other causes as the competing event. All statistical tests were two-sided. RESULTS: A total of 11.4% of patients developed cardiotoxicity. Risk factors for cardiotoxicity included increased cumulative dose of epirubicin (hazard ratio per every 100 mg/m(2) administered = 1.40, 95% confidence interval = 1.21 to 1.61), patient age, predisposition to cardiac disease, history of mediastinal irradiation, or antihormonal treatment for metastatic disease. Risk factors for death from all other causes (including breast cancer) included lesser dosages of epirubicin, increased tumor burden, prior use of adjuvant chemotherapy, and patient age. The cumulative dosage of epirubicin that carries a 5% risk of cardiotoxicity was lower than previously assumed and was dependent on risks of both cardiotoxicity and overall mortality. CONCLUSION: Maximum cumulative dosages of epirubicin are presented that confer a 5% risk of cardiotoxicity for patients with different sets of risk factors.

[Current status of the neo-adjuvant and adjuvant therapy for the resectable non-small cell lung cancer].

Generally, the surgical resection has been considered to be the standard therapy for the clinical Stage I-IIIA non-small cell lung cancer (NSCLC). However, the 5 year-survival rate has been reached approximately less than 20%. To improve the prognosis, especially for the Stage IIIA NSCLC, many clinical trials have been performed to assess the availability of the chemotherapy or radiation therapy in the preoperative or postoperative period. Although some clinical trials concerning about the neo-adjuvant therapy have reported the improvement of the postoperative survival rate, the availability of both neo-adjuvant and adjuvant therapy is still controversial. Further assessment for the well designed phase III clinical trials will be necessary to establish the availability of such modalities for the treatment of respectable NSCLC.

[Chemoradiotherapy in locally advanced cancers of the uterine neck. Retrospective study of 92 patients treated at the Institute Curie between 1986 and 1998]]. / Chimioradiothérapie dans les cancers du col utérin localement évolués. Etude rétrospective de 92 patientes traitées à l'institut Curie de 1986 à 1998.

PURPOSE: The prognosis of locally advanced cervix cancers is poor with metastatic and local recurrence risks. Recent publications reported that concurrent chemotherapy and pelvic radiation increased local control compared to radiotherapy alone. Chemotherapy could also decrease metastatic recurrences. We report 92 cases of patients with locally advanced cervix cancer treated between 1986 and 1998 at the Institut Curie. PATIENTS AND METHODS: Concurrent chemoradiation was exclusive in 51 cases and added to surgery in 41 cases. Chemotherapy with 5FU-Cisplatin-Mitomycin C-Vindesin (protocol A) was performed for 43% of patients and 57% of them received 5FU-Cisplatin alone (protocol B). RESULTS: Median follow-up was 64 months (6-149 months). Five-year disease-free survival rate was 47% and local control rate was 70%. Disease-free survival was correlated with therapeutic response. After exclusive chemoradiation, the good responsive patients had a better DFS (54% vs 26%, p = 0.018). In the surgery group, those patients with sterilized lymph nodes and tumours had also a higher DFS (76% vs 47%, p = 0.036). Toxicity was higher with protocol A. CONCLUSION: From our study, it appears that local control of advanced cervix cancers is better with combined chemoradiotherapy but disease-free survival stays low according to the metastatic evolution. Metastasis without local recurrence remained frequent in our study. 5FU-CDDP chemotherapy has a lower toxicity and is as effective as 5FU-CDDP-Mitomycin C-Vindesin protocol, in association with radiotherapy.

Chemotherapy and concomitant irradiation in inflammatory breast cancer.

The purpose of this study was to evaluate the efficacy of concurrent chemotherapy and irradiation in inflammatory breast cancer (IBC). Between January 1990 and December 1998, forty-eight non-metastatic patients with clinical or occult IBC were treated with chemotherapy and irradiation. The induction chemotherapy consisted of epirubicin, cyclophosphamide and vindesin, in association with split-course bi-fractionated irradiation to a total dose of 65 Gy with concomitant cisplatin and fluorouracil. Maintenance chemotherapy consisted of high-dose methotrexate and 6 cycles of epirubicin, cyclophosphamide and fluorouracil Hormonal treatment was given routinely but mastectomies were not routinely performed. A high rate of locoregional control was obtained in 47 evaluable patients of whom 93.6 % achieved a complete clinical response. Three patients had locoregional relapses, always with concomitant metastatic dissemination. In 47 patients, 21 developed metastatic dissemination with a median delay of 23 months. Median disease-free survival (DFS) was 45 months. Median overall survival (OS) has not yet been reached after a median follow-up of 44.5 months. The 3-year DFS rate was 53 % and the 3-year OS rate was 71 %. Toxicity was mainly hematological. During the induction therapy, grade 3 or 4 neutropenia occurred in 54 % of patients, grade 3 or 4 thrombocytopenia in 23 % and grade 3 or 4 anemia in 8 %. The administration of induction chemotherapy and concomitant irradiation is feasible in patients with IBC. The hematological toxicity of this treatment approach is significant but nevertheless, the treatment achieves a high degree of locoregional control and improved survivaL

Evaluation of catecholamine metabolites, mIBG scan, and bone marrow cytology as response markers in stage 4 neuroblastoma.

BACKGROUND: The early biological response has been proved an excellent predictor in acute lymphoblastic leukemia and nephroblastoma. We asked whether catecholamine metabolites, mIBG scan, and bone marrow evaluation might be relevant response markers in disseminated neuroblastoma. PROCEDURE: Three hundred sixty-seven unselected stage 4 neuroblastoma patients treated according the German cooperative trial NB90 were entered into the study. Catecholamine plasma and urine levels were centrally determined by gas chromatography/ mass spectrometry. Bone marrow cytology and mIBG scans were evaluated by local investigators. RESULTS: At diagnosis, mIBG scan was positive in 306 patients (92%), borderline in seven patients (2%), and negative in 19 patients (6%). Bone marrow aspirates were cytologically positive in 292 patients (84%) and negative in 57 patients (16%). Plasma catecholamine levels were elevated in 79% (206 of 260 patients.), urinary levels in 91% (307 of 338 patients). The outcome of patients with normalized mIBG scan after four courses of chemotherapy [5 year EFS (event free survival) 0.22 +/- 0.07] was not superior to the outcome of patients with still abnormal uptake (5 year EFS 0.30 +/- 0.05). The event free survival of patients with still positive bone marrow aspirates after four courses (0.16 +/- 0.06) was inferior to the EFS of patients with negative bone marrow aspirates (0.26 +/- 0.04, P = 0.0054). Urinary catecholamine normalization after four cycles of chemotherapy (5 year EFS 0.35 +/- 0.06 versus 0.26 +/- 0.10) had no influence on outcome, whereas plasma catecholamine normalization after the first (5 year EFS 0.40 +/- 0.09 versus 0.14 +/- 0.07, P= 0.0364) or the fourth cycle (5 year EFS 0.35 +/- 0.06 versus 0.26 +/- 0.10, P = 0.0242) indicated a better outcome. CONCLUSIONS: These data show that serial plasma catecholamine levels and bone marrow aspirates in the course of the disease are useful tools in predicting outcome.

Cisplatin-based chemotherapy for postoperative recurrence in non-small cell lung cancer patients: relation of the in vitro chemosensitive test to clinical response.

The usefulness of the in vitro chemosensitivity test, the collagen gel droplet embedded culture drug- sensitivity test (CD-DST, Int J Oncol 11: 449, 1997), in cisplatin-based combined chemotherapy for postoperative recurrent tumors in non-small cell lung cancer (NSCLC) patients was retrospectively analyzed. CD-DST data for cisplatin (or carboplatin), etoposide, 5-fluorouracil, mitomycin C, and vindesine were obtained in 311 surgically resected primary lesions. Of them, 25 patients were practically treated with first-line cisplatin- or carboplatin-based chemotherapy for postoperative initial recurrence. Nine (36%) of them responded to the combined chemotherapy for recurrent lesions, including one with complete remission, whereas 16 did not, with no change in 5 and progression in 11. Seven (70%) of 10 patients receiving combined chemotherapy using two or three in vitro sensitive chemoagents showed good responses, whereas there was no responder among the patients receiving chemotherapy including no in vitro sensitive chemoagents. In particular, of 11 patients showing good sensitivity to cisplatin or carboplatin on CD-DST, 8 (73%) responded to chemotherapy, whereas only one (7%) of 14 patients showing cisplatin- or carboplatin-resistance on CD-DST was a responder. Thus, CD-DST results for the chemoagents, especially cisplatin or carboplatin, correlated with chemotherapeutic response, indicating that the CD-DST analysis of surgically resected primary NSCLC tumors is a practically useful indicator of the clinical effect of first-line cisplatin-based combined chemotherapy for postoperative recurrence.

[Clinical observation on effect of chemotherapy combined with Chinese medicine in treating advanced tumor patients and on immunologic parameters].

OBJECTIVE: To observe the effects of chemotherapy combined with Chinese herbal medicine (Spleen-Kidney tonifying) in treating advanced tumor patients and on immune parameters. METHODS: One hundred and one advanced tumor patients were randomly divided into the treated group (54 patients) treated by Chinese medicine combined with chemotherapy, and the control group (47 patients) treated by chemotherapy alone. After being treated for 8 weeks (2 treatment courses), the changes of tumor size, body weight, Karnofsky scores, immunologic parameters, peripheral blood cells, as well as the toxic and side-effects were also studied. RESULTS: Improvement of various degree was obtained on the immunologic parameters such as CD3, CD4, CD4/CD8, NK cells, and the quality of life, as Karnofsky score in the treated group, in comparing with those in the control group the difference was significant (P < 0.05, P < 0.01). But on behalf of the toxic and side-effects in advanced patients, there was no significant difference between the two groups. CONCLUSION: Chemotherapy combined with Chinese Spleen-Kidney tonifying drugs could improve the immunologic functions in the advanced tumor patients.

[Postoperative complications after radiochemotherapy or chemotherapy for bronchial cancers]. / Complications post opératoires après radiochimiothérapie ou chimiothérapie des cancers bronchiques.

OBJECTIVE: The purpose of this study was to evaluate the risk of lung cancer surgery, following induction chemo and/or radiotherapy. METHODS: This retrospective study included 69 patients treated from January 1990 to January 1998 for a primary lung cancer in whom surgery had been performed after induction treatment. Surgery had not been considered initially for the following reasons: N2 disease (IIIA; n = 25), temporary functional impairment (2 stages IB and 2 stages IIIA [N2]; n = 4); doubtful resectability (stage IIIB [T4]; n = 40). The medical regimen resulted in combined radio-chemotherapy in 43 patients who received 2 to 4 cycles of chemotherapy (average = 2.9 +/- 0.8 cycles) and 43 +/- 8 Gy (20 to 60 Gy), or chemotherapy alone in 26 patients (3 +/- 0.7 cycles). RESULTS: Exploratory thoracotomy was performed in 4 patients (6%). The in-hospital mortality was 9% (n = 6) from respiratory origin in all cases. There were 4 reoperations (6%): 3 for bronchial fistula and 1 for bleeding. Thirty five patients (51%) required blood transfusion (4.5 +/- 3.8 cell packs). The incidence of early and delayed bronchial fistula after pneumonectomy was 15%. Thirteen patients had a postoperative pneumonia (19%). CONCLUSION: Surgery for lung cancer after induction chemo and/or radiotherapy is associated with an increased risk. While the mortality seems "acceptable", the morbidity rate however is high.

[Curative treatment of non-metastatic esophageal cancer: concomitant chemoradiotherapy and high-dose-rate endoluminal curietherapy boost]. / Traitement à visée curative du cancer de l'oesophage non métastatique: chimio-radiothérapie concomitante et surdosage par curiethérapie endoluminale à haut débit de dose.

OBJECTIVES: The aim of this study was to evaluate the feasibility, toxicity, and efficacy of a curative combination of chemo-radiotherapy with high-dose-rate brachytherapy (HDRB) in patients with non metastatic esophageal cancer. PATIENTS AND METHODS: Fifty-two patients with esophageal carcinoma were treated with > 50 Gy external irradiation, concomitant chemotherapy (5FU-CDDP) followed by HDRB delivering 12.5 Gy (6-20) as a boost. Twelve patients were stage I, 20 stage IIa, 5 stage IIb, and 13 stage III, 1 Tis, 1 stage N unknown. Surgery was not indicated for medical reasons. RESULTS: The response rate was 96%, with complete response rate 85%. The 1-, 3-, 5-year overall survival rates were 78%, 33%, and 22% respectively. A local failure occurred in 32%, and distant metastasis in 16%. Severe (grade 3, 4) acute toxicity occurred in 6 cases, severe late toxicity in 2 cases and there was 1 toxic death. Tumoral length > or = 5 cm and stage IIa, IIb and III versus stage 1 indicated poor prognosis. CONCLUSION: This regimen is feasible and well tolerated. The 5-year overall survival is 22%, but the local failure rate is still very high. These results are encouraging and will be prospectively evaluated with currently ongoing randomized trial.

Multi-institutional phase II randomized trial of integrated therapy with cisplatin, dacarbazine, vindesine, subcutaneous interleukin-2, interferon alpha2a and tamoxifen in metastatic melanoma. BREMIM (Biological Response Modifiers in Melanoma).

The aim of this study was to evaluate the toxicity and efficacy of a monochemotherapy regimen of dacarbazine (DTIC), tamoxifen , interferon-alpha2a and interleukin-2 (IL-2) and two polychemotherapy regimens of cisplatin, DTIC, vindesine, tamoxifen, interferon-alpha2a with or without IL-2 in patients with metastatic melanoma. Consecutive patients with metastatic melanoma were enrolled in this trial and were randomized to arm A, consisting of DTIC 800 mg/m2 every 21 days, IL-2 9 MIU subcutaneously days 1-5 and 8-12, arm B, consisting of cisplatin 30 mg/m2 days 1-3, DTIC 250 mg/m2 days 1-3 and vindesine 2.5 mg/m2 day 1 every 28 days (CVD), or arm C, consisting of CVD plus IL-2 6 MIU days 1-5 and 8-12 every 28 days. In all three arms Interferon 3 MU subcutaneously three times a week and tamoxifen 20 mg orally were given throughout. Ninety-two patients were included in this study. Patient characteristics in the three groups were well balanced. The three regimens were delivered on an outpatient basis without major toxicity. The toxicities that did occur consisted primarily of flu-like symptoms in the IL-2 arms (A and C) and haematological toxicities in the CVD arms (B and C). No grade IV toxicities were encountered and no treatment-related deaths occurred. The total response rate was 13% in arm A, 35% in arm B and 37% in arm C. The median duration of response was 6 months and the median survival was 11 months. According to this phase II randomized trial polychemoimmunotherapy with CVD has an objective response rate of 35-36%, while monochemoimmunotherapy with DTIC has a response rate of 13%.

Lack of effectiveness of adjuvant alternating chemotherapy in node-positive, estrogen-receptor-negative premenopausal breast cancer patients: results of a multicentric Italian study. The Breast Cancer Adjuvant Chemo-Hormone Therapy Cooperative Group (GROCTA).

A multicentric randomized trial was performed in premenopausal women with node-positive, estrogen-receptor-negative breast tumors to assess the potential superiority of alternating adjuvant chemotherapy over 'standard' CMF chemotherapy. Between January 1989 and June 1992, 107 patients were entered into the study and randomly allocated to receive either cyclophosphamide 100 mg/m2 per as on days 1-14, methotrexate 40 mg/m2 and 5-fluorouracil 600 mg/m2 intravenously (i.v.) on days 1, 8 (CMF), every 4 weeks for a total of 6 cycles, or the following regimens: CMF as previously; epidoxorubicin 75 mg/m2 i.v. on day 1 and vincristine 0.75 mg/m2 i.v. on days 1, 8 (EV); mitomycin-C 10 mg/m2 i.v. on day 1 and vindesine 2 mg/m2 i.v. on days 1, 8 (MVs). The three regimens were given every 4 weeks for a total of 6 cycles according to the following schedule: CMF, EV, MVs, CMF, EV, MVs. At a median follow up of 48 months (range 30-72), 40 patients have relapsed and 17 have died overall. More patients in the triple-combination arm have relapsed and more have died, the latter difference tending toward statistical significance (p = 0.06). There was no statistical difference in the site of relapse between the two groups. Total duration of adjuvant therapy was similar in the two arms (312 chemotherapy cycles in the triple arm and 308 in the CMF arm). Treatment toxicity was also comparable, although more patients in the triple-combination arm were still regularly menstruating 6 months after the completion of chemotherapy. This study failed to show any advantage ensuing from the use of alternating chemotherapy in patients with early breast cancer.

[Effective combined injection method of fluoropyrimidine and platinum--application for advanced esophageal cancer].

In patients with esophageal cancer, combined chemotherapy is usually given as a part of multimodality treatment and therefore undesirable toxicity should be diminished. Recently, the most standard protocol against esophageal cancer has been Cisplatin/5-FU combination, of which the response rate is 40-60%. We showed the development of chemotherapy and chemoradiotherapy using Cisplatin/5-FU for esophageal cancer. In recent Japanese protocols, continuous infusion of Cisplatin for several days or bolus injection of low-dose Cisplatin are supposed to be mainstream. The supra additive effect of leucovorin to Cisplatin +5-FU considering biochemical modulation is confirmed, and Cisplatin/5-FU/adriamycin protocol study is ongoing.

Neoadjuvant chemotherapy with cisplatin-vindesine-5-fluorouracil and folinic acid for locally advanced head and neck carcinoma.

The aim of this study was to establish the feasibility, evaluate the response rate, and assess the impact on local control and survival in locally advanced (bulky nodal) squamous cell carcinoma of the head and neck (SCCHN) patients treated with neoadjuvant chemotherapy consisting of cisplatin followed by continuous infusion of vindesine and fluorouracil with intermittent i.v. folinic acid. Eligibility criteria included histologically proven SCCHN, previously untreated locally advanced stage III-IV with measurable or evaluable disease, no distant metastases, an Eastern Cooperative Oncology Group (ECOG) performance status of less than 2, patient age of at least 18 years, and adequate bone marrow, hepatic, and renal functions. The protocol consisted of three cycles (day 1, day 21, day 42) of Cisplatin (CDDP) 100 mg/m2/day i.v. on day 1 immediately followed by 4 days (96 h) of continuous infusion of vindesine 0.8 mg/m2/day and 5-fluorouracil (5-FU) 600-700 mg/m2/day with folinic acid 150 mg/m2 i.v. every 6 h x 16 doses before locoregional treatment with radiotherapy preceded by radical surgery when appropriate. Twenty-nine patients were enrolled in this study, and 28 were evaluable for activity; an objective response rate of 55% (four complete responses, 12 partial responses) was achieved. Leukopenia and mucositis were the most frequent and severe toxicities. The addition of vindesine did not improve the activity of the CDDP-FU-folinic acid combination, but this may be partly because of the particularly poor prognosis of the present patient population, with 75% of stage IV bulky nodal disease (N2c-N3).

[Diagnosis and therapeutic management of gastric lymphomas]. / Diagnóstico y manejo terapéutico de los linfomas gástricos.

PURPOSE: The optimal management of primary gastric non-Hodgkin's lymphoma (PGL) remains controversial. The purpose of this paper is to describe the histopathology, clinical behavior and management of 15 patients with PGL. PATIENTS AND METHODS: All patients were diagnosed of PGL in our Center from January 1985 to September 1995. Resection specimens were reexamined and cases were reclassified according to the concept of MALT-derived lymphoma. Age, sex, symptoms, localization, stage, treatment, complications and response were reported. RESULTS: 9 patients had low-grade B-cell lymphoma of MALT type, 5 had high-grade B-cell lymphoma (one with evidence of low-grade lymphoma of MALT type) and 1 had centroblastic-centrocytic B-cell lymphoma. Seven cases were diagnosed by endoscopy biopsies, 8 through laparatomy specimens. Stage was I in 3 cases, II1 in 5, II2 in 5, III in 0 and IV in 2. 13 patients had undergone primary gastric resection: 10 received additional chemotherapy and 1 radiotherapy. The two cases with stage IV have died: one died after surgery and one relapsed immediately after chemotherapy. After a median follow-up of 40 months, 13 patients are alive: 11 in complete response and 2 in relapse. Minor surgical complications occurred in 12 patients and major complications in 6 patients. CONCLUSIONS: Gastric resection still plays an important role in the management of early-stage PGL. Chemotherapy can be an effective therapeutic procedure in unresected or surgical high-risk patients.