Phase II study of cisplatin and dacarbazine for metastatic colorectal carcinoma resistant to 5-fluorouracil.

Twenty-six patients with metastatic colorectal cancer were given cisplatin (CDDP) and dacarbazine (DTIC). Patients who relapsed while receiving adjuvant 5-fluorouracil (FU) or had 5-FU-resistant metastatic disease were included. Median age was 52 years and the male-to-female ratio was 1. Performance status (ECOG) was 3 in 5 patients and 0-2 in the remainder. CDDP (20 mg/m2/day i.v.) and DTIC were given (250 mg/m2/day i.v.) on days 1-5. The treatment was repeated every 3 weeks until disease progression. Total response rate was 19.2% (95% confidence interval: 4.5-34.3%) with one clinical complete response (3.8%) and 4 partial responses (15.4%). Median response duration was 5 months. Median survival for the whole group and for responders was 6 and 8 months, respectively. In conclusion, CDDP + DTIC combination has modest activity in patients with colorectal cancer resistant to 5-FU treatment.

Diagnostic value of ferritin in the differential diagnosis of malignant effusions.

UNLABELLED: The diagnostic value of ferritin in pleural effusions or ascites was studied in 151 samples from 147 patients (four patients had both kind of effusions). Samples (99 pleural effusions, 52 ascites) were evaluated in 4 groups: benign transudate (27 cases), benign nontuberculous exudate (26 cases), tuberculous exudate (47 cases) and malignant exudate (51 cases). Median ferritin levels in effusions were 67 ng/ml, 805 ng/ml, 889 ng/ml, 998 ng/ml and median effusion/serum (E/S) ratios were 0.7. 2.0, 4.9, 3.2 respectively. There was a significant difference between the concentrations of ferritin in malignant (51 cases) and nonmalignant effusions (100 cases) (p < 0.001), but the specificity and positive predictive value were low (43% and 45% respectively). Ferritin levels in transudate group were significantly lower than those in the others (p < 0.001). However, ferritin concentrations in three exudate groups were similar (p > 0.05). When compared the all inflammatory effusions (malignant, tuberculous, nontuberculous inflammatory exudates) with noninflammatory effusions (transudate and exudate), we determined a significant difference (p < 0.001). CONCLUSIONS: 1) Elevated ferritin concentration in effusions is significant indicators of exudates; 2) It is not good a parameter to discriminate the malignant effusions from the benign ones; 3) They can be useful in the differential diagnosis of the inflammatory exudations from the noninflammatory ones.

Results of the cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) +/- bleomycin treatment and evaluation of prognostic factors in aggressive lymphomas in Turkey.

Prognostic factors and the results of the cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) +/- bleomycin treatment in 93 consecutive evaluable patients with aggressive lymphomas are presented. The overall response rate, excluding 7 patients with primary extranodal lymphoma who were in complete remission after surgery, was 83% with a complete response (CR) rate of 69%. Overall survival (OS) rates of all patients and disease-free survival (DFS) rates of complete responders at 4 years were 52 and 66%, respectively. Almost two thirds of the patients could be given at least 75% of the planned chemotherapy doses. Treatment toxicities were in acceptable limits, only 10% of the patients had grade 3-4 hematological toxicity. Age, performance status (PS), stage, number of extranodal sites (ENS) (< or = 1 vs. > 1), B symptoms, serum LDH levels were evaluated as prognostic factors. Univariate survival analysis yielded stage, ENS and PS as significant prognostic factors for OS (p = 0.0009, p = 0.0028 and p = 0.0155, respectively). Only involvement of more than 1 ENS was strongly associated with low CR (p = 0.0479) and high relapse rates (p = 0.0118), and it was also determined as the only independent prognostic factor for OS in patients younger than 60 (p = 0.0015). A modified age-adjusted prognostic index, including ENS in addition to stage, LDH and PS, was found to be more significant than the original age-adjusted International Prognostic Index (IPI) for both DFS (p = 0.0030) and OS (p < 0.00001). In conclusion, modified age-adjusted index may be a convenient alternative to the original age-adjusted IPI to identify high-risk patients with aggressive lymphomas in Turkey and probably also in other developing countries for experimental intensive regimens.

Phase II study of a modified combination of etoposide, doxorubicin, and cisplatin for patients with advanced gastric cancer.

BACKGROUND: Based on the promising results of EAP (etoposide, doxorubicin, and cisplatin) combination, a phase II study of modified EAP combination was performed in patients with advanced gastric cancer to evaluate the response, toxicity, and survival. METHOD: Fifty-two consecutive patients with measurable or evaluable advanced gastric cancer, who had no prior therapy except surgery, were treated every 28 days with etoposide 120 mg/m2/day, doxorubicin 25 mg/m2/day, and cisplatin 40 mg/m2/day on days 1 and 8, intravenously. Forty-seven patients were evaluable for response and toxicity. RESULTS: Overall response rate was 40.5% (95% CI = 37-54.7%), including 12.8% complete response. Responses were higher in patients with locally advanced disease (57.89%) as compared to those with distant metastases (28.57%) (P = 0.044). The median overall survivals of the entire group and the responders were 7 months and 11 months, respectively. Complete responders had significantly longer response duration and overall survival (31.5 months and 45.5 months, respectively), as compared to partial responders (6 months and 9 months, respectively). Six of the responders (31.6%) were alive at 2 years. Disease extension and pretreatment performance status had significant effects on survival. Grade 3-4 toxicity was observed in 33% of patients. There were no deaths related to toxicity. CONCLUSIONS: EAP as used in this trial is an effective treatment in advanced gastric cancer. The effect is more pronounced in patients with locally advanced disease.

Two dose levels of ifosfamide in malignant mesothelioma.

Thirty-one consecutive patients with histologically proven and symptomatic malignant mesothelioma were treated with two dose levels of ifosfamide. The first group of 15 patients were given 2.3 g/m2/day for 5 days (group A) and the following 16 patients were treated with 1.2 g/m2/day for 5 days of ifosfamide (group B). Treatment cycles were repeated every 3 weeks. While the partial response rate (PR) in group A was 38.5%, it was only 6.25% in group B (P > 0.05). The 95% confidence interval for the difference in PR rates was 3.3-61.2% > The overall survival (OAS) of groups A and B were similar (8 months and 9 months, respectively). Higher Grade 3-4 myelotoxicity was observed in group A when compared to group B (30.8% vs. 18.7%; P > 0.05). In conclusion, a favourable response rate could be achieved in malignant mesothelioma with high dose ifosfamide at the cost of increased toxicity.

Mesna/ifosfamide, mitoxantrone, etoposide, bleomycin, vincristine, prednisone (MINE-BOP) combination chemotherapy in the treatment of refractory and relapsed non-Hodgkin's lymphoma.

Twenty-one consecutive patients with refractory or relapsed non-Hodgkin's lymphomas were treated with a novel combination chemotherapy (MINE-BOP), comprising myelosuppressive (ifosfamide, mitoxantrone, etoposide) and non-myelosuppressive (bleomycin, vincristine and prednisone) drugs. Median age of the patients was 42 years and all had intermediate or high-grade lymphoma. Fifteen patients had refractory disease. All patients had previously been treated with one or two regimens, containing anthracyclines. In all cases the duration between the last chemotherapy and the MINE-BOP regimen was shorter than 12 months. Response rate was 57% with 33% complete remission (CR). Median disease-free and overall survivals were 7 and 10 months respectively. The serum LDH level was the only significant prognostic factor in this study. The toxicity of this regimen was moderate with 24% of febrile neutropenia and 9% of microscopic hematuria. Toxic death due to febrile neutropenia was observed in one patient who had bone marrow involvement. To conclude, the addition of non-myelosuppressive drugs to the chemotherapy regimen and shortening the interval between the application of cytotoxic drugs as used in the present study did not show any improvement of response and survival in this group of patients.

Severe vascular toxicity associated with cisplatin-based chemotherapy.

A 19-year-old man with a germ cell tumor who experienced hypertension, acute myocardial infarction, and cerebrovascular accident (CVA) associated with hypomagnesemia as late complications of cisplatin-based chemotherapy is presented, and previously reported cases in the literature are reviewed. Different physiopathologic mechanisms are hypothesized for early and late vascular complications of cisplatin.

Primary gastrointestinal lymphomas in Turkey: a retrospective analysis of clinical features and results of treatment.

UNLABELLED: Thirty-three patients with primary gastrointestinal lymphoma (GIL) followed at Ankara University Medical School have been evaluated. The most frequent locations of the disease are the small intestine (48.4%) and the stomach (39.3%). The intermediate and high grade lymphomas constitute 84.8% of the cases. The mean age of the patients with small intestinal lymphoma is 28.7 years and 47.1 years for those with gastric lymphoma. The patients treated with surgery and chemotherapy (S+CT) have a longer survival than those treated with chemotherapy (CT) alone. IN CONCLUSION: 1) Small intestinal lymphoma occurs more frequently than gastric lymphoma in our study. 2) The median age of the Turkish patients with primary GIL is approximately 10 years less than those in the Western countries. 3) The therapeutic results of S+CT are superior to those of CT in the early stages of the disease.

Cisplatin plus VP-16 combination chemotherapy in advanced refractory breast cancer.

Twenty-nine patients with advanced refractory breast cancer were treated with cisplatin 20 mg/m2/d and VP-16 100 mg/d for 5 days every 3-4 weeks. Ten patients received mitomycin C 10 mg/m2 every 6 weeks additionally. Partial response was obtained in 10 of 26 evaluable patients (38%). The response rates for the group treated with and without mitomycin C were 40% and 37.5%, respectively. Median response duration was 5.5 months in partial responders. Median survival was 9.5 months for partial responders and 2 months for the rest of the patients. Cisplatin and VP-16 combination can be considered as a salvage treatment in heavily pretreated patients with advanced breast cancer.

Treatment of metastatic malignant melanoma with 24 hours continuous venous infusion of dacarbazine and cisplatin.

Twenty consecutive patients with metastatic malignant melanoma were treated with a combination of 24 hours continuous infusion of dacarbazine (250 mg/m2) and cisplatin (20 mg/m2) for 5 days every 3 weeks. One patient (5%) achieved a complete response (CR) and 3 patients (15%) obtained a partial response (PR) with an overall response rate of 20%. Minimal response was observed in 5 other patients (25%). Complete response duration was 8 months. Median response duration of partial responders was 7 months. Median survival of all responders (CR+PR) was 8.5 months. Toxicity was mild to moderate.