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Biomedical subjects

R Somers

Publications and source records attributed to R Somers.

At least 73 records · Page 4Linked to original sources

Superiority of second over first generation chemotherapy in a randomized trial for stage III-IV intermediate and high-grade non-Hodgkin's lymphoma (NHL): the 1980-1985 EORTC trial. The EORTC Lymphoma Group.

A first-generation CHOP-like cyclic combination chemotherapy (CT) regimen using cyclophosphamide 600 mg/m2 IV d1, hydroxorubicin (doxorubicin) 50 mg/m2 IV d1, VM26 60 mg/m2 IV d1, and prednisone 40 mg/m2 PO d1-5 (CHVmP) was compared to a second-generation combination wherein vincristine 1.4 mg/m2 IV and bleomycin 6 mg/m2 IM/IV were added at mid-interval (d15) to the former drugs (CHVmP + VB) in the treatment of intermediate- and high-grade malignant NHL. From April 1980 to January 1986, 141 eligible patients with stage III-IV unfavorable histologies (except T lymphoblastic NHL) entered this EORTC randomized trial. In both arms adjuvant radiotherapy (30 Gy) was given in instances of bulky or residual disease. In all patient subsets the outcome favored the second-generation regimen. The difference was even greater in patients with Diffuse Large Cell Lymphoma (DLCL). At 5 years, overall survival was 53% with CHVmP + VB versus 29% (p = 0.002). The advantage was due to a higher complete remission (CR) rate (80% versus 50%, p = 0.01). Indeed, once CR was achieved the relapse-free survival (RFS) was not significantly influenced (59% versus 49%). No significant additional toxicity could be attributed to vincristine and bleomycin. This study demonstrates a clear benefit for intermediate- and high-risk malignant NHL and particularly DLCL from intercalating non-myelotoxic drugs at mid-cycle intervals, without adverse effects.

Adolescent↗

Ifosfamide plus doxorubicin in previously untreated patients with advanced soft tissue sarcoma. The EORTC Soft Tissue and Bone Sarcoma Group.

The objective of this phase II trial was to assess the therapeutic activity and toxicity of doxorubicin plus ifosfamide in previously untreated patients with advanced soft tissue sarcoma. Treatment was doxorubicin 50 mg/m2 followed by a 24 h infusion of ifosfamide 5 g/m2 plus mesna 2.5 g/m2 repeated every 3 weeks until disease progression or unacceptable toxicity occurred. Of 203 patients entered, 175 were evaluable for response. The response rate was 35% (95% CI 28-42%), with 9% of the patients achieving a complete remission and 26% a partial remission. The median time to progression was 29 weeks for all evaluable patients, and 67, 40 and 28 weeks for complete and partial responders and patients with stable disease, respectively. The median duration of survival was 58 weeks. Myelosuppression was the dose-limiting toxicity, resulting in leukopenia (WHO grade 3 and 4) in 73% of evaluable treatment courses. Other side-effects were rare and usually well manageable.

Adolescent↗

Causes of death after therapy for early stage Hodgkin's disease entered on EORTC protocols. EORTC Lymphoma Cooperative Group.

The risk of dying from different causes after Hodgkin's disease (HD) therapy has been quantified from a series of 1,449 patients with early stages included in four successive clinical trials conducted by the European Organization for Research and Treatment of Cancer (EORTC) Lymphoma Cooperative Group since 1963. Overall, 240 patients died and the 15-year survival rate was 69% whereas the expected rate was 95%. The standardized mortality ratio (SMR) technique was used to quantify excess deaths as a function of time since first therapy. At each interval, SMR was significantly increased, giving: 0-3 year, 8.86 (p less than 0.001); 4-6 year, 9.25 (p less than 0.001); 7-9 year, 7.08 (p less than 0.001); 10-12 year, 9.53 (p less than 0.001); 13-15 year, 4.37 (p less than 0.01); and 16+ years, 3.80 (p less than 0.05). While the proportion of deaths as a consequence of HD progression, treatment side-effect, and intercurrent disease decreased with time, that of second cancer and cardiac failure peaked during the 10-12 year post-treatment interval. After 15 years of follow-up, the risk of dying from causes other than HD continued to increase. These findings indicate that although probably cured from HD, patients are at higher risk for death than expected, a risk that might be a consequence of therapy.

Adult↗

Effective systemic therapy for spinal epidural metastases from breast carcinoma.

A complete resolution of spinal epidural metastases following systemic therapy, consisting of chemotherapy and/or hormonal therapy, is reported in four patients with breast carcinoma. Remissions were of substantially longer duration than previous remissions induced by radiotherapy. Single systemic therapy is an underestimated way of treatment for spinal epidural metastases. This way of treatment should be considered when radiotherapy has failed. Under certain circumstances it might even be considered as primary treatment. The protracted remissions following systemic therapy, even in the case of a complete myelographic block, warrant further clinical studies concerning this mode of treatment.

Adult↗

Increased risk of lung cancer, non-Hodgkin's lymphoma, and leukemia following Hodgkin's disease.

The risk of second cancers (SCs) was assessed in 744 patients with Hodgkin's disease (HD) admitted to The Netherlands Cancer Institute from 1966 to 1983. Sixty-nine SCs were observed one month or more after start of first treatment. These included 14 cases of lung cancer, nine cases of non-Hodgkin's lymphoma (NHL), 16 cases of leukemia, and six cases of the myelodysplastic syndrome (MDS). The median interval between the diagnosis of HD and that of second lung cancer, NHL, and leukemia was 8.1, 13.3, and 5.7 years, respectively. The overall relative risks (RR) (observed/expected [O/E] ratios) of developing lung cancer, NHL, and leukemia were 4.9 (95% confidence limit [CL], 2.7 to 8.2), 31.0 (95% CL, 14.2 to 58.9) and 45.7 (95% CL, 26.1 to 74.2), respectively. At 15 years the cumulative risk of developing an SC amounted to 20.6% +/- 2.9%. The 15-year estimates of lung cancer, NHL, and leukemia were 6.2% +/- 1.9%, 5.9% +/- 2.1% and 6.3% +/- 1.7%, respectively. Increased lung cancer risk following HD has not frequently been clearly demonstrated before; that we were able to demonstrate such risk may be due to the completeness of follow-up over long periods that could be achieved in this study. Excess lung cancer risk was only noted in treatment regimens with radiotherapy (RT); also, all lung cancers arose in irradiation fields. Excess risk of leukemia was only found in treatment regimens involving chemotherapy (CT). For NHL, combined modality treatment was shown to be the most important risk factor. Risk of lung cancer and NHL increased with time since diagnosis. A time-dependent covariate analysis (Cox model) performed on leukemia and MDS showed an increasing risk with intensity of CT, age (greater than 40 years), and a splenectomy.

Adult↗

Management of non-Hodgkin lymphoma in adults in Scandinavia, United Kingdom, and The Netherlands. Report from the European School of Oncology intercity meeting at Huddinge Hospital, 3rd June, 1988.

Current treatment strategies in northern Europe of non-Hodgkin lymphoma are presented. High-grade malignant lymphomas have been treated with doxorubicin-containing polychemotherapy in various modes. The advantage of six-drug regimens over CHOP-like therapy is as yet not proven. Patients with the ability to tolerate the calculated dose have good prognosis. High-dose therapy and bone marrow transplantation should be considered in poor-risk patients with lymphoblastic lymphomas in first remission, patients with all high-grade histologies in partial remission after first-line therapy and patients with relapse that are still responsive to therapy. Preliminary results from autologous bone marrow transplantation in follicular lymphoma are also encouraging. Chlorambucil induces multiple remissions in follicular lymphoma, with a median duration of the 1st, 2nd and 3rd remission being the same. The watch and wait strategy seems justified initially in most asymptomatic generalized low-grade malignant lymphomas. Systemic therapy is required in aggressive stage II-IV lymphomas. A meticulous investigation is needed for stage I patients before giving local treatment only. Immune phenotyping is of great value for diagnosis and staging. Liver, but not bone marrow involvement seems to be an adverse prognostic factor. Follicular lymphoma is an example of a dynamic tumour with gradual cellular changes associated with new and more malignant clinical signs.

Antineoplastic Combined Chemotherapy Protocols↗

Review of the clinical trials activity of the Soft Tissue and Bone Sarcoma Group of the European Organization for Research and Treatment of Cancer.

Despite the low incidence of sarcomas, the Soft Tissue and Bone Sarcoma Group has established itself as one of the more active cooperative groups of the European Organization for Research and Treatment of Cancer. Performing over a 10 yr period three phase III protocols (total entry 750 patients), three randomized phase II studies (464 patients), a pilot combination study (185 patients), and 12 phase II studies (406 patients). The new randomized phase III protocol for advanced soft-tissue sarcoma will provide an interesting test of the validity of the current membership policy, which has not discouraged the participation of enthusiastic new members. For extremity sarcomas, improved surgical techniques have increased the number of patients retaining functional limbs but have maintained excellent rates of local control. However, systemic metastasis remains a significant problem and presents a challenge for future adjuvant studies.

Adult↗

Treatment results of primary stage I and II non-Hodgkin's lymphoma of the stomach.

Gastric lymphoma in stage I or II was usually treated by partial gastrectomy and total abdominal irradiation in our institute since 1970. Since 1978, a number of patients were also treated without laparotomy, in clinical stage I with radiotherapy only and in clinical stage II with combined modality treatment. Treatment results of 58 patients are reported. A relapse-free survival rate of 85% was reached for 24 patients treated with resection and irradiation either in stage I or II, and for seven patients in stage I who did not undergo surgery. For these patients, survival in stage I was 85%, in stage II, however, survival dropped to 60% due to intercurrent deaths. Seven stage II2 patients received intensive chemotherapy and radiotherapy with 58% relapse-free survival. Twenty patients could not be treated according to the outlined treatment protocol. For the total group, survival in stage I is 65% and in stage II 35%. In the Addendum, an additional group of 17 patients is mentioned with the same result.

Actuarial Analysis↗

Comparison of total nodal irradiation versus combined sequence of mantle irradiation with mechlorethamine, vincristine, procarbazine, and prednisone in clinical stages I and II Hodgkin's disease: experience of the European Organization for Research and Treatment of Cancer.

The H5 study of supradiaphragmatic Hodgkin's disease in clinical stages I-II consisted of two controlled trials adapted to patients considered to have either favorable or unfavorable characteristics, based on prognostic factors identified in two former studies by the European Organization for Research and Treatment of Cancer. Of 494 patients, 257 who were classified as having unfavorable prognosis qualified for the more intensive treatment and consequently were spared a staging laparotomy. They were randomized either to total nodal irradiation (TNI) (132 patients) or to treatment with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) alternated with mantle irradiation (MOPP X 3-mantle irradiation-MOPP X 3; 3M) (125 patients). In complete responders (96%), the 6-year relapse-free survival was 77% in the TNI arm and 91% in the 3M arm (P = .02). Relapses in the initially involved and irradiated mantle area were less frequent in patients started on MOPP. The 6-year actuarial total survival (TS) (TNI, 82%, and 3M, 89%; P = .05) appeared to favor the 3M arm, but this difference disappeared when patients dying from causes unrelated to cancer were excluded from analysis. In men less than or equal to 40 years old, there was no difference in relapse-free survival, freedom from disease progression, or TS between the groups receiving TNI and 3M. Thus, TNI is a short and appealing treatment, especially because it preserves fertility. The same observation was true in women less than or equal to 40 years old. In addition, even irradiation less than TNI, which is meant to spare the ovaries, provided a TS similar to that for 3M.

Adult↗