Carboplatin in association with etoposide and either adriamycin or epirubicin for untreated small cell lung cancer: A dose escalation study of carboplatin

A multi-center, open trial was conducted to determine the maximal tolerable dose of carboplatin in combination with conventional doses of both etoposide and an anthracycline for the treatment of previously untreated small cell lung cancer (SCLC) patients. Ninety-five patients [48 with limited disease (LD) and 47 with extensive disease (ED)¦ received a total of 376 courses of treatment. Carboplatin was given on day 1 at a dose of 250 mg m^?2 in 60 courses, 300 mg m^?2 in 69, 330 mg m^?2 in 236 and 350 mg m^-2 in 11, with 120 mg m^?2 etoposide on days 1, 3 and 5 and either 40 mg m^-2 adriamycin or 60 mg m^?2 epirubicin on day 1. Epirubicin was not administered before carboplatin reached the dose of 330 mg m^?2. Courses were repeated every 3 weeks. The main toxicity was hematological. The first course of therapy induced a dose-dependent decrease of leucocyte, neutrophil and platelet counts: all patients, except one, who received 350 mg m^?2 carboplatin had a neutropenia below 200 μ^?1 and a thrombopenia below 100,000 μl^?1. Three patients died of septicemia. Other toxicities were well tolerated. After three courses, patients were re-staged by performing a mandatory fiberoptic bronchoscopy and a thoracic computed axial tomography (CAT). The overall objective response rate for 86 evaluable patients was 91% (98% for LD) with 21% complete remissions (30% for LD). All 23 hepatic and six brain sites, evaluable after chemotherapy alone, responded. This new combination, in which the recommended dose of carboplatin is 330 mg m^?2, should be evaluated in a prospective study for SCLC.     

FDG PET utility in paraneoplastic sweet syndrome

We describe a 43-year-old woman who presented a sudden onset of fever and migratory arthralgias. Physical examination revealed tender, well-demarcated erythematous papules and plaques, consistent with a Sweet syndrome. After developing systemic symptoms with hepatomegaly, a liver biopsy and FDG PET imaging demonstrated the presence of an aggressive and extended non-Hodgkin T-cell lymphoma. This case highlights the usefulness of FDG PET imaging for the screening of this paraneoplastic syndrome.     

Carboplatin in association with etoposide and either adriamycin or epirubicin for untreated small cell lung cancer: a dose escalation study of carboplatin. UCL Clinical Oncology Group

A multi-center, open trial was conducted to determine the maximal tolerable dose of carboplatin in combination with conventional doses of both etoposide and an anthracycline for the treatment of previously untreated small cell lung cancer (SCLC) patients. Ninety-five patients [48 with limited disease (LD) and 47 with extensive disease (ED)] received a total of 376 courses of treatment. Carboplatin was given on day 1 at a dose of 250 mg m-2 in 60 courses, 300 mg m-2 in 69, 330 mg m-2 in 236 and 350 mg m-2 in 11, with 120 mg m-2 etoposide on days 1, 3 and 5 and either 40 mg m-2 adriamycin or 60 mg m-2 epirubicin on day 1. Epirubicin was not administered before carboplatin reached the dose of 330 mg m-2. Courses were repeated every 3 weeks. The main toxicity was hematological. The first course of therapy induced a dose-dependent decrease of leucocyte, neutrophil and platelet counts: all patients, except one, who received 350 mg m-2 carboplatin had a neutropenia below 200 microliters-1 and a thrombopenia below 100,000 microliters-1. Three patients died of septicemia. Other toxicities were well tolerated. After three courses, patients were re-staged by performing a mandatory fiberoptic bronchoscopy and a thoracic computed axial tomography (CAT). The overall objective response rate for 86 evaluable patients was 91% (98% for LD) with 21% complete remissions (30% for LD). All 23 hepatic and six brain sites, evaluable after chemotherapy alone, responded.(ABSTRACT TRUNCATED AT 250 WORDS)     

LNH-84 regimen: a multicenter study of intensive chemotherapy in 737 patients with aggressive malignant lymphoma

From July 1984 to September 1987, 737 patients with aggressive malignant lymphoma (ML) were treated by an intensive regimen (LNH-84) comprising three or four courses of doxorubicin, 75 mg/m2; cyclophosphamide, 1,200 mg/m2; vindesine, 2 mg/m2 x 2; bleomycin, 10 mg x 2; and prednisolone, 60 mg/m2 x 5 (ACVB), consolidation with high-dose methotrexate, ifosfamide, etoposide, asparaginase, and cytarabine, and a randomized late intensification with two courses of cytarabine, cyclophosphamide, teniposide, bleomycin, and prednisone (AraCVmB). Four hundred forty-two patients had intermediate-grade ML, 221 highgrade ML, and 74 unclassified ML. Most of the patients had advanced disease: stage IIE (23%), III (13%), or IV (47%); 38% disseminated nodes; 38% two or more extranodal sites; and 41% a tumoral mass greater than 10 cm. Five hundred fifty-three patients (75%) went into complete remission (CR), 63 (9%) into partial remission, 62 (8%) failed to respond, and 59 (8%) died during ACVB courses, 17 of them from progression of the disease. With a median follow-up of 23 months, the estimated 2-year overall survival time to failure (TTF), and time to relapse (TTR) survival are 67%, 56%, and 67%, respectively. Patients receiving a late intensification had the same relapse rate as the other patients. A persistent fibronecrotic mass was found in 150 patients (20%) and did not influence the relapse rate. Toxicity was mainly neutropenia and infection during the ACVB courses, with 40 patients (5%) dying from septic complications while responding to treatment. Fifty-three percent of the patients had a neutropenia less than 0.500 x 10(9)/L, 58% fever (6% grade 4), and 49% a documented infection (8% grade 4). These results obtained with the LNH-84 regimen demonstrate that this therapeutic scheme is an effective treatment for aggressive ML.     

Late intensification chemotherapy with autologous bone marrow transplantation in selected small-cell carcinoma of the lung: a randomized study

A multicentric randomized prospective trial was conducted to test whether late intensification chemotherapy would increase the remission rate, the relapse-free survival, and the survival of small-cell lung cancer patients responding to induction chemotherapy. Autologous bone marrow transplantation was used as support to reduce the duration of the aplasia induced by very high-dose chemotherapy. As induction chemotherapy, 101 patients received, during a period of 5 months, a total dosage of 120 mg/m2 methotrexate, 4.5 mg/m2 vincristine, 1,800 mg/m2 cyclophosphamide, 180 mg/m2 doxorubicin, 160 mg/m2 cisplatin, 750 mg/m2 VP-16-213, and 30 Gy prophylactic cranial irradiation. Forty-five patients, selected for their sensitivity to this induction treatment, were randomized to a last cycle of chemotherapy that combined cyclophosphamide, BCNU, and VP-16-213 either at a conventional dosage of 750 mg/m2 intravenously (IV), 60 mg/m2 IV, and 600 mg/m2 orally or alternatively at a very high dosage of 6 g/m2 IV, 300 mg/m2 IV, and 500 mg/m2 IV, respectively. In the late intensification group, the complete remission rate increased from 39% before randomization to 79% after high-dose chemotherapy. Median relapse-free survivals after randomization for intensified and control chemotherapy groups were 28 and 10 weeks, respectively (P = .002). Median overall survival after induction therapy was 68 weeks for the intensified group compared with 55 weeks for the conventional therapy group (P = .13). Four patients died during intensification. Patients in both groups relapsed at the primary site. It can thus be concluded that late intensification chemotherapy for sensitive small-cell lung cancer increases the complete remission rate and resulted in a statistically significant increase in the relapse-free survival. However, since relapse occurred at the primary site and toxicity was high, overall survival was not significantly improved.