Palmar-plantar erythrodysesthesia due to docetaxel-capecitabine therapy is treated with vitamin E without dose reduction.

Palmar-plantar erythrodysesthesia (PPE) is a distinctive and relatively frequent toxic reaction related to some chemotherapeutic agents. Doxorubicin, cytarabine, docetaxel, fluorouracil, and capecitabine are the most frequently implicated agents. Recently, taxanes, especially docetaxel, have been widely used in combination with capecitabine in patients with metastatic breast cancer (MBC). A high percentage of PPE has been seen in patients undergoing this combination therapy. PPE seems to be dose dependent and both peak drug concentration and total cumulative dose determine its occurrence. Withdrawal or dose reduction of the implicated drug usually gives rise to amelioration of the symptoms. Supportive treatments such as topical wound care, elevation, and cold compresses may help to relieve the pain. Use of systemic corticosteroids, pyridoxine (vitamin B6), blood flow reduction, and, recently, topical 99% dimethyl-sulfoxide have been used with variable outcomes. Vitamin E treatment has not been published before, especially without dose reduction of docetaxel-capecitabine therapy. Here we present five MBC patients treated with docetaxel-capecitabine combination therapy in whom PPE was observed during the clinical follow-up period. In all patients grade 2-3 PPE was observed. Vitamin E therapy was started at 300 mg/day p.o. without dose reduction of therapy and after 1 week of treatment PPE began to disappear. We suggest that it could be of interest to consider vitamin E as a preventive drug when drugs with a strong association with PPE are going to be administered.

Cisplatin plus oral etoposide (EoP) combination is more effective than paclitaxel in patients with advanced breast cancer pretreated with anthracyclines: a randomised phase III trial of Turkish Oncology Group.

Our objective was to determine whether oral etoposide and cisplatin combination (EoP) is superior to paclitaxel in the treatment of advanced breast cancer (ABC) patients pretreated with anthracyclines. From December 1997 to August 2003, 201 patients were randomised, 100 to EoP and 101 to paclitaxel arms. Four patients in each arm were ineligible. The doses of etoposide and cisplatin were 50 mg p.o. twice a day for 7 days and 70 mg m(-2) intravenously (i.v.) on day 1, respectively, and it was 175 mg m(-2) on day 1 for paclitaxel. Both treatments were repeated every 3 weeks. A median of four cycles of study treatment was given in both arms. The response rate obtained in the EoP arm was significantly higher (36.3 vs 22.2%; P=0.038). Median response duration was longer for the EoP arm (7 vs 4 months) (P=0.132). Also, time to progression was significantly in favour of the EoP arm (5.5 vs 3.9 months; P=0.003). Median overall survival was again significantly longer in the EoP arm (14 vs 9.5 months; P=0.039). Toxicity profile of both groups was similar. Two patients in each arm were lost due to febrile neutropenia. The observed activity and acceptable toxicity of EoP endorses the employment of this combination in the treatment of ABC following anthracyclines.

Anticipated administration of GM-CSF in the treatment of non small cell lung cancer.

The purpose of this study was to verify the kinetic response of the human marrow myeloid progenitor cells to the short term use of GM-CSF and its impact on the therapeutic activity of this three-drug cisplatinum containing regimen in non small cell lung cancer (NSCLC). Sixty patients with stage III-B and IV NSCLC were randomised to receive GM-CSF for 3 days, five days prior to the onset of chemotherapy. The chemotherapy regimen consisted of Mitomycin-C: 6 mg/m2 on day one, Ifosfamide: 2000 mg/m2 days 1 to 3, Mesna: 2000 mg/m2 days 1 to 3, Cisplatinum: 30 mg/m2 days 1 to 3, and was repeated every 4 weeks. All the patients received 30-50 Gy of radiotherapy to the primary and/or metastatic sites. There were positive correlations between stage of the disease, chemosensitivity of the tumor, number of chemotherapy cycles and overall survival (p=0.000). Administration of GM-CSF was an independent prognostic parameter in locally advanced and metastatic disease (p=0.041). In the GM-CSF receiving arm more courses could be given (117 versus 99, p=0.0415), and less courses were postponed (6 versus 22). In this arm, the mean of granulocyte nadir was higher (p=0.033) and mean time to granulocyte recovery became shorter (p=0.001) as the number of chemotherapy cycles increased. It was concluded that, dose intensification with GM-CSF prophylaxis is benefical in increasing the treatment tolerability by decreasing the intensity of granulocytopenia as well as providing rapid recovery.

Environmental malignant mesothelioma in southern Anatolia: a study of fifty cases.

Malignant mesothelioma is a highly aggressive tumor of the serous membranes, which in humans results from exposure to asbestos and asbestiform fibers. Although occupational malignant mesothelioma is still the most common form of this lesion, naturally contaminated soil can play an important role in the development of environmental malignant mesothelioma in some parts of the world. Fifty cases of malignant mesothelioma (MM) from southern Turkey with no occupational history of asbestos exposure were reviewed regarding pathologic and clinical features. A case of hyaline fibrous plaque of the pleura was also included in this series. Histologically the cases were classified as epithelial (36 cases); sarcomatous (7 cases); and biphasic (7 cases). One of the sarcomatous cases was desmoplastic. Ultrastructural examination of the tumor tissue in three cases revealed long-surface microvilli in epithelial cells. Interstitial cells of the lung in one case showed electron-dense asbestos fibers in the cytoplasm. Mineralogical analyses of the lung tissue in three cases of MM and the case of pleural plaque showed high amounts of asbestos fibers most consistent with tremolite and actinolite. The clinical and pathologic features of our cases support that the environmental inhalation of asbestos is still a major health problem in some parts of Turkey.

Primary therapeutic decision-making in inoperable non-small cell lung cancer.

PURPOSE: To test the accuracy of our treatment decisions for patients with inoperable non-small cell lung cancer (NSCLC) using a prototype decision-support system (DSS) and a prognostic index (PI). METHODS AND MATERIALS: To predict patient outcome and select optimal treatment, the systems protocol was tested retrospectively in 242 patients with Stage I-IV disease. The PI was determined in 184 patients with Stage I-IIIa,b disease. Survival was the final determinant of the accuracy of our treatment decisions. RESULTS: Until 1996 it was our treatment policy to treat all Stage III patients with radical intent unless they had symptoms requiring palliation. In 1997, after the palliation concept of the DSS and the PI were changed to include all Stage III disease, there was considerable discordance between the rates of palliative treatment indicated by the DSS and the PI (69% and 99%, respectively) as well as that observed in our practice (30% in the DSS group and 20% in the PI group, respectively). There was also a significant difference in survival between the patients in the low- and high-risk categories defined by the PI (median survival of 12 versus 6 months, respectively; p = 0.0001). In the group that received radical radiotherapy, there was also a significant difference in the duration of survival between the low- and high-risk groups (median survival of 12 versus 8 months, respectively; p = 0.01). In addition, the risk categories proved to be the most important predictor of survival in the patients receiving radiotherapy longer than 2 weeks (median survival of 12 versus 7 months, respectively; p = 0.0001). In high-risk patients, however, the duration of radiotherapy did not have a significant impact on survival (p = 0.25). CONCLUSION: Our data indicate that the PI is a useful method for selecting radical or palliative treatment modalities as well as for determining treatment duration.

Supportive treatment in weight-losing cancer patients due to the additive adverse effects of radiation treatment and/or chemotherapy.

The reversal of anorexia and weight loss especially in patients with advanced cancer suffering from radiation treatment (RT) -related complications and debilitated furtherly during RT would be a welcome relief. The purpose of this study is to evaluate the feasibility of supportive treatment with megestrol acetate (MA) in our weight-losing cancer patients increasingly experiencing anorexia, smell, taste, and weight loss due to the additive adverse effects of RT +/- chemotherapy and how MA changes the additive role of the severity of RT reactions on such patients. From June 1997 to October 1998, 100 eligible patients were enrolled on a randomized, placebo-controlled clinical trial. Of the 100 patients, 46 received MA during RT and 4 after the end of the RT, and 50 received placebo for 3 months. Subjective parameters were assessed by a brief questionnaire form based on scoring from 1 to 5, according to the degree of the loss or change for each parameter of malnutrition, appetite, taste and smell developed by us. At the end of the study a statistically significant weight gain was achieved in the patient group receiving MA compared to the placebo group (+3 to +5 kg versus -3.7 to -5.9 kg, p=0.000). Significant improvements were seen in performance status (p=0.000), appetite (p=0.000), malnutrition (p=0.000), loss of taste (p=0.000) and smell qualities (p=0.02) in the MA group compared to the placebo group. In the MA group there was no statistically significant difference related to the weight changes according to the grade of either the acute or late RT effects (p=0.65 and 0.07, respectively). Whereas, in the placebo group a statistically significant additive effect of the acute and late RT effects was detected on weight loss (p=0.008 and 0.007, respectively). We observed no side-effects of MA in a 3-month time follow-up. The use of MA 480 mg/day during RT was effective in reversing anorexia and weight loss in spite of the acute RT effects, and helped most patients to well tolerate specific tumor therapy. Further evaluation of its mechanisms of action on RT-related adverse effects, tumor response relationships, and effect on patient survival are researched.

Impact of tumor stage, operative down-staging, tumor grade and radioresponsitivity of the tumor on survival in supratentorial astrocytomas.

This retrospective study analyzed specifically the predicting factors for radioresponse and survival in 74 supratentorial astrocytoma patients. As a result of this study, cytoreduction in terms of ODs to T1 or T0 stage level or pre-RT T1 tumor stage along with radioresponse has a positive impact on long-term survival. It seems that radical radiotherapy should be the choice of treatment for the patients who had pre-RT T0 and T1 disease who were found more likely to respond to radiotherapy. This has not been reported previously and needs to be confirmed in larger trials.

Relationship of Helicobacter pylori infection to several malignant and non-malignant gastrointestinal diseases.

The importance of the Helicobacter pylori infection was investigated as a risk factor for several gastrointestinal diseases. In this study 203 patients with gastric cancer, 61 with peptic ulcus, 60 with gastritis and 100 asymptomatic control subjects were investigated. Serum samples were examined for IgC antibodies to H. pylori by enzyme linked immunoassay - tissue samples were stained for H. pylori by Wartin-Stary technique and by Giemsa for routine histopathology. H. pylori seropositivity was 58.1% in gastric cancer, 54% in peptic ulcus, 63.3% in gastritis and 27% in asymptomatic control group. There was a 10.1% discordance between the serum and tumor determinants in the seropositive group and 11.3% of discordance in the seronegative group. The frequency of H. pylori seropositivity was lowest in cardia tumors (22.7%) and highest in antral tumors (65.5%, p=0.00002). H. pylori seropositivity was 29% in diffuse type of histology, 35% in mixed type and 79% in the intestinal type (p=0.00000). In the gastric cancer patients the frequent use of salty food (p=0.00001, OR=6.4), excessive salt, pickled food (p=0.0000, OR=24.92) and proteins (p=0.003, OR=0.45) were more significant than asymptomatic volunteers. In gastric cancer patients the frequent use of salty and pickled food were relevantly associated with H. pylori infection (p=0.001). It was concluded that H. pylori infection could play a role in the pathogenesis of non-malignant gastrointestinal diseases which may be the precursor of carcinoma. However, other contributing factors to carcinogenesis must be investigated.

Refractory breast cancer: a comparison of two different chemotherapy regimens.

Sixty metastatic and recurrent breast cancer patients who had been given cyclophosphamide, methotrexate and fluorouracil (CMF) therapy previously and were treated at the Oncology Departments of Cukurova and Ege University Medical Schools between March 1992-94, were randomized into 2 groups for the chemotherapy program. The 30 patients in the 1st group were given etoposide: 200 mg x day x 5 days orally every 3 weeks. The 30 patients of the 2nd group were given fluorouracil: 500 mg x m2, doxorubicin: 5O mg/m2, cyclophosphamide: 500 mg/m2 intravenously every 3 weeks. The response rates were 21/30 in group 1 and 17/30 in group 2. The median duration of responses was 11 months (8-21) in the 1st and 9 months (4-18) in the 2nd group. Severe myelotoxicity was observed in 2 of the patients in the 1st group and in 5 of the patients in the 2nd group.

The use of recombinant human granulocyte colony-stimulating factor in combination with single or fractionated doses of ifosfamide and doxorubicin in patients with advanced soft tissue sarcoma.

Sixty patients with stage III-B and IV soft tissue sarcomas were randomized to receive either ifosfamide 5 g/m2xdx1 and doxorubicin 60 mg/m2xdx1 given every 3 weeks (arm A) or ifosfamide 1.8 g/m2xdx5 and doxorubicin 60 mg/m2xdx1 given every 4 weeks (arm B). Recombinant human granulocyte colony-stimulating factor (r-met Hu G-CSF: 250 micrograms/m2xd) was applied with a prophylactic intent to patients in arm A only. The response rate was higher in arm A patients (56% versus 33%, p = 0.03). In stage III patients, the complete response rate was significantly higher (53% versus, 13.3%, p = 0.01) and the duration of response was significantly longer in arm A (20 +/- 8.2 months versus, 13.4 +/- 7 months, p = 0.05). Chemotherapy related myelotoxicity and mucositis were also less frequent in this arm as a result of prophylactic r-met Hu G-CSF administration (p = 0.04, p = 0.003). It was concluded that single dose ifosfamide and doxorubicin combinations deserve further investigation under the cover of hematopoietic growth factors, particularly in patients with stage III soft tissue sarcomas.

A randomised trial of two cisplatin-containing chemotherapy regimens in patients with stage III-B and IV non-small cell lung cancer.

Seventy-four newly diagnosed patients with histologically proven Stage III-B and IV non-small cell lung cancer were randomized to receive either cisplatin: 20 mg/m2 x day x 5, ifosfamide: 1.8 g/m2 x day x 5, mesna: 1.2 g/m2 x day x 5, etoposide: 100 mg/m2 x day x 5 (ICE) or cisplatin: 20 g/m2 x day x 5 and etoposide: 100 mg/m2 x day x 5. Response rates were 59% in the ICE and 40% in the CE arm with a significant advantage in response duration and overall survival in the ICE receiving patients (P = 0.03, P = 0.0008). As we used granulocyte colony stimulating factor (G-CSF) very frequently, myelotoxicity remained substantial but acceptable.

Human papillomavirus in pterygium.

Between August 1991 and 1992 consecutive pterygium cases and eight normal conjunctival tissues were examined for the presence of polyclonal Human Papilloma Virus (HPV) antigen by the avidin-biotin-complex technique and 16 of the pterygium cases and 25 pc of the control conjunctivas revealed HPV positivity. In six of the HPV positive pterygium tissues, there were also an epithelial proliferation. In conclusion, HPV infection was not endemic, but sporadic in Cukurova region, and it may be contributed to development of pterygium. In addition, because it is seen together with six cases of epithelial hyperplasia, it seems to play an important role in the development of neoplasia and such patients need to be followed up for possible malignant transformation.

A randomized study comparing cyclophosphamide, doxorubicin, vincristine (CAV) with cyclophosphamide, etoposide, vincristine, methotrexate (CEVM) in patients with small cell lung cancer.

This trial was carried out to assess the response rate and survival benefit achieved, if any, by substitution of etoposide for doxorubicin and addition of methotrexate in combination with cyclophosphamide and vincristine in the treatment of 113 patients with small cell lung carcinoma (SCLC). Cyclophosphamide, etoposide, vincristine, methotrexate (CEV-M) yielded a response rate of 75% in localized disease (LD) and 63% in extensive disease (ED), versus 61% in LD and 52% in ED in the cyclophosphamide, doxorubicin, vincristine (CAV) arm. There was also a significant survival benefit for the responders in favor of CEV-M (21.7 +/- 3.8 months of median survival compared to 13.6 +/- 2.8 months in CAV arm) in patients with LD.