Immunohistochemical expression of human epidermal growth factor receptor (HER)-4 and prognosis in patients with metastatic breast cancer.

PURPOSE: The clinical value of HER4 - a cell surface receptor that belongs to the human epidermal growth factor receptor family - for predicting survival outcomes in patients with breast cancer remains controversial. Herein, we sought to investigate the prognostic significance of HER4 immunohistochemical expression with respect to progression-free survival (PFS) and overall survival (OS) in Turkish patients with metastatic breast cancer (MBC). METHODS: MBC patients (N=45; mean age=50.5±12.7 years) were consecutively enrolled between 2000 and 2006 in the Department of Oncology at the Uludag University Medical Center, Bursa, Turkey. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded sections. The predictive value of HER4 expression was investigated by multivariate analysis after allowance for potential confounders. RESULTS: The mean PFS in the study participants was 11.35 months (range:1-50), whereas the median OS was 22.18 months (range:1-76). The mean PFS in patients with a HER4 immunohistochemical score of 0, 1+, 2+, and 3+ was 11.0 ± 4.8, 11.3 ± 7.7, 11.7 ± 8.1, and 10.4 ± 7.4 months, respectively (p=0.99) . The mean OS in patients with a HER4 score of 0, 1+, 2+, and 3+ was 13.3 ± 6.8, 25.6 ± 10.8, 22.9 ± 10.7, and 13.5 ± 9.9, months, respectively (p=0.44). The results of multivariate Cox regression analysis indicated that the presence of visceral metastases was the only independent prognostic factor for both OS (HR=3.01, 95% CI=1.56-3.99, p <0.01) and PFS (HR=2.91, 95% CI=1.51-3.78, p <0.01). CONCLUSION: HER4 immunohistochemical expression is not an independent predictor of OS and PFS in Turkish MBC patients.

Epidemiology of colorectal cancer in Turkey: A cross-sectional disease registry study (A Turkish Oncology Group trial).

BACKGROUND/AIMS: This study aimed to determine the epidemiological characteristics of colorectal cancer in Turkey. MATERIALS AND METHODS: In this multicenter, prospective, and cross-sectional registry study, data for 968 patients with colorectal cancer from 21 centers in 7 geographic regions were analyzed. RESULTS: Diagnosis was colon cancer in 662 (68.4%) and rectum cancer in 306 (31.6%) patients. In total, 60.9% of patients was male; mean age was 58.9±12.6 years. Among patients, 15.0% was drinking alcohol, 17.5% was smoking, 1.5% had familial history of polyposis, 15.0% had diabetes mellitus, 1.0% had inflammatory bowel disease. Fruit and vegetable consumption was low (<3 times/week) in 35.5% and red meat consumption was high (≥3 times/week) in 47.4% of the patients. Median time-to diagnosis was 3.0 months and 4.0 months for patients with colon and rectum cancer, respectively. Mean body mass index was >25 in all group of patients. Distal rectum (61.3%) and sigmoid colon (36.8%) were the most common locations of cancer, for rectum and colon respectively. In total, 85.6% of patients were operated; 25.8% had emergency surgery. Low anterior resection rate was 64.2% in rectum cancer. In majority (89.8%) of the patients with rectum cancer who received preoperative treatment, conventional chemo-radiotherapy regimen was given. pTNM staging at diagnosis showed that stage III and IV patients were in majority (35.9% and 29.7%, respectively). CONCLUSION: Colon cancer is more frequent than rectum cancer in Turkey. Colorectal cancer patients are diagnosed at later stages. Most of the cases were operated. Interregional differences for risk factors are worthwhile for evaluation in future trials.

Clinical significance of adiponectin expression in colon cancer patients.

PURPOSE: Surgery is the definitive treatment for early colon cancers. Adjuvant therapies are used with the aim of eradicating micrometastases and improving cure rates. Recent studies have proposed that adiponectin might be responsible for obesity-related malignancies. We investigated the prognostic value of this cytokine. MATERIALS AND METHODS: Patients who underwent surgical removal of stage II or III (TNM staging) primary tumors and were followed for at least three years were included in the study given adequate specimen for immunohistochemical evaluation. Based on these criteria, 53 patients were included. RESULTS: Mean age was 58.3 ± 10.1 years (35-78 years). The mean follow-up time was 41 months (10-96 months). Immunohistochemical evaluation identified 21 patients (39.6%) with cytoplasmic adiponectin present in their specimens. The rates of recurrence were 42.9% (9/21) and 34.4% (11/32) in patients with and without adiponectin expression, respectively. In cases with adiponectin expression, mean disease - free survival was 60.3 ± 9.03 months, and in cases without adiponectin expression, mean disease - free survival was 68.7 ± 6.67 months (P = 0.414). Mean overall survival of patients with adiponectin expression was 65 months compared to 67 months for patients without (P = 0.786). CONCLUSION: Adiponectin, which is secreted by adipose tissue, may have a role in the development and progression of cancer via its pro-apoptotic and/or anti-proliferative effects. Adiponectin expression in tumor tissues is likely to have a negative effect on disease - free survival in patients with stage II/III colon cancer; however, no statistically significant effect was demonstrated.

Lack of prognostic significance of adiponectin immunohistochemical expression in patients with triple-negative breast cancer.

INTRODUCTION: Triple-negative breast cancers (TNBCs) - which lack the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) - have no established markers that can be used for prognostic stratification. As adiponectin has been previously implicated in a more aggressive phenotype of primary breast cancer, we explored the relation between adiponectin immunohistochemical expression and prognosis in TNBCs. MATERIAL AND METHODS: Immunohistochemical staining for adiponectin was performed in 38 TNBC patients. Disease-free survival (DFS) and overall survival (OS) served as the main outcome measures. RESULTS: Of the 38 TNBC patients, 18 (47%) had negative and 20 (53%) positive adiponectin immunohistochemical expression. We did not find any significant association between adiponectin immunohistochemical expression and the baseline characteristics. In addition, there were no associations between adiponectin immunohistochemical expression and prognosis. CONCLUSIONS: Although our results suggest that adiponectin immunohistochemical expression is not of prognostic significance in TNBCs, further studies are warranted to determine the role of this adipokine in breast cancer biology.

Prognostic significance of human epidermal receptor (HER)- 3 immunohistochemical expression in patients with metastatic breast cancer.

BACKGROUND: Previous reports have shown that human epidermal receptor (HER)-3 overexpression may be associated with poor prognosis in patients with breast cancer, but results have been conflicting. In this study, we sought to investigate the prognostic significance of HER-3 immunohistochemical expression in patients with metastatic breast cancer. METHODS: We retrospectively analyzed HER-3 immunohistochemical expression profiles in 45 paraffin-embedded specimens from patients who had been treated between 1996 and 2006 in the Department of Oncology of the Uludag University School of Medicine, Bursa, Turkey. Membranous or cytoplasmic dominant expression patterns of HER-3 were analyzed using the Rajkumar score and a cytoplasmic 4-point scoring system, respectively. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. RESULTS: The median PFS in the study participants was 9 months (interquartile range: 4.5-13 months), whereas the median OS was 20 months (interquartile range: 7.5-28 months). Categorization of the patient population according to HER-3 positive immunohistochemical expression did not reveal any statistically significant difference in terms of both PFS (p=0.70) and OS (p=0.81). The results of multivariable Cox regression analysis indicated that tumor size was the only independent predictor of PFS, whereas estrogen and progesterone receptor status was independently associated with OS. CONCLUSIONS: HER-3 immunohistochemical expression did not correlate with outcomes in Turkish patients with metastatic breast cancer. Although our results suggest that HER-3 expression in cancer specimens is not of prognostic significance, further prospective studies are warranted to confirm these results.

Prognostic significance of c-erbB2 overexpression in patients with metastatic gastric cancer.

BACKGROUND: Overexpression of the gene c-erbB2, which encodes a receptor tyrosine kinase, has been associated with prognosis and response to therapy in several solid tumors. This study was designed to test whether c-erb-B2 overexpression can be related to prognosis of patients with metastatic gastric cancer. METHODS: Between 2005 and 2010, 46 cases of metastatic gastric cancer were evaluated immunohistochemically for c-erb-B2 overexpression. Overall survival (OS) and time-to-progression (TTP) served as the main outcome measures. RESULTS: c-erbB2 was overexpressed in 19 (41.3 %) cases and 8 patients (17.4 %) had a c-erbB2 score of 3+ (a strong complete membrane staining observed in >10 % of the tumor cells). c-erbB2 expression was not associated with the clinicohistological characteristics of the study participants. The mean OS was 11.48 ± 1.03 months, whereas the mean TTP was 8.28 ± 0.8 months. Compared with patients with a score of 2+ or less (n = 38), those with a c-erbB2 score of 3+ (n = 8) had both a significantly lower OS (15.55 ± 1.63 vs. 8.22 ± 0.88 months, respectively, p < 0.05) and TTP (10.72 ± 1.81 vs. 6.11 ± 0.61 months, respectively, p < 0.05). After allowance for potential confounders, Cox regression analysis identified a c-erbB2 score of 3+ as an independent predictor of both OS (hazard ratio = 1.9; 95 % confidence interval = 1.1-3.7, p < 0.05) and TTP (hazard ratio = 1.8; 95 % confidence interval = 1.1-4.1, p < 0.05). CONCLUSION: Our results suggest that c-erbB-2 overexpression may have a prognostic significance in patients with metastatic gastric cancer.

The SOCS-1 -1478CA/del polymorphism is not associated with colorectal cancer or age at onset in Turkish subjects.

BACKGROUND: Suppressor of cytokine signaling (SOCS)-1 acts as a key regulator of many cytokine signaling pathways and its abnormal expression has been identified in several human malignancies, suggesting potential roles in carcinogenesis. The aim of this study was to investigate any association between the functional SOCS- 1 -1478CA>del polymorphism and colorectal cancer (CC) as well as age at onset in a Turkish clinical sample. MATERIALS AND METHODS: A total of 122 subjects were enrolled in this case-control study (70 CC cases and 52 controls). The SOCS-1 -1478CA>del polymorphism was genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: The odds ratio of the del allele for CC relative to the CA allele was not significantly different between the groups (OR=0.71, 95% CI=0.41-1.22, p=0.27). This result did not change after adjustment for age and sex on multivariable regression analysis (OR=0.84, 95% CI=0.59-1.34, p=0.53). When the SOCS-1 -1478CA>del polymorphism was analyzed among CC patients in relation to the age at disease onset, we found no significant differences between subjects with the del/del, CA/del, and CA/CA genotypes. CONCLUSIONS: The results of our study did not point towards a major role of the SOCS-1 -1478CA>del polymorphism in the pathogenesis of CC in Turkish subjects.

Pulmonary actinomycosis mimicking metastasis from lung adenocarcinoma.

BACKGROUND: Pulmonary actinomycosis may create a diagnostic and therapeutic dilemma especially in cancer patients. CASE REPORT: A 64-year-old male patient presented with a productive cough, bloody sputum, and weight loss. Thoracic computed tomography (CT) showed a 5-cm mass in the upper lobe of the right lung, and a 2-cm mass in the lower lobe of the left lung. Bronchoscopic examination did not show any endobronchial lesions. CT-guided needle biopsy of the right pulmonary lesion showed lung adenocarcinoma. Wholebody positron emission tomography/CT revealed an increase in fluorodeoxyglucose accumulation in the upper lobe of the right lung, in the lower lobe of the left lung, and in the right hilar and paratracheal lymph nodes. Before chemotherapy was initiated, the patient had to be admitted to the hospital because of massive hemoptysis. Bronchoscopic examination indicated persistent bleeding in the left lower lobe bronchus. The patient underwent diagnostic left thoracotomy, and wedge resection of the lower lobe mass. The diagnosis was pulmonary actinomycosis, and the patient received oral amoxicillin. He underwent successful surgery for the primary disease following 6 cycles of chemotherapy. CONCLUSION: Oncologists should be aware of rare diseases that may affect management approaches in the treatment of cancer.

Primary small cell carcinoma of the breast: report of seven cases and review of the literature.

AIMS AND BACKGROUND: The aim of the study was to analyze the clinicopathological characteristics, treatment modalities, and clinical outcome of patients with primary small cell carcinoma of the breast. METHODS: Fifty-three cases of primary small cell carcinoma of the breast were identified; 7 cases in this series and 46 from the English-language medical literature. RESULTS: There were 52 females and 1 male. The mean age was 53 years. Tumor size ranged from 1 to 18 cm (mean, 4.53). Axillary node metastasis was present in 61.7%. Only one patient had distant metastases at presentation. The presence of hormone receptors was reported in 24.5% of the tumors. Modified radical mastectomy was the most common surgical procedure and was performed in 50.9% of the patients. Adjuvant radiotherapy was administered to 39.6% of the patients, and 69.8% underwent chemotherapy. Thirteen percent of patients received adjuvant tamoxifen therapy. The mean follow-up was 20.75 months (range, 3-60), and 10 of 53 cases (18.9%) died of metastatic disease. CONCLUSIONS: The prognosis of primary small cell carcinoma of the breast largely depends on the initial stage of the disease. Multimodality treatment including surgery, radiotherapy and chemotherapy seems to be the most appropriate strategy for early disease. Chemotherapy is usually unsuccessful in treating metastatic disease.

Lack of genotoxicity in medical oncology nurses handling antineoplastic drugs: effect of work environment and protective equipment.

OBJECTIVE: In this study we aimed to investigate the genotoxic effects of antineoplastic agents in occupationally exposed oncology nurses. Genotoxic effects mean the disruptive effects in the integrity of DNA and they are associated with cancer development. Biomonitoring of health care workers handling antineoplastic agents is helpful for the evaluation of exposure to cytostatics. PARTICIPANTS: The study included an exposed and two control groups. The exposed group (n=9) was comprised of oncology nurses. The first (n=9) and second (n=10) control groups were comprised of subjects who did not come into contact with antineoplastic drugs working respectively in the same department with oncology nurses and in different departments. METHODS: Genotoxicity evaluation was performed using SCE analysis. After applying culture, harvest and chromosome staining procedures, a total of 25 metaphases were analyzed per person. Kruskal Wallis test was used to perform statistical analysis. RESULT: A statistically significant difference of sister chromatid exchange frequencies was not observed between the exposed and control groups. CONCLUSION: Lack of genotoxicity in medical oncology nurses might be due to good working conditions with high standards of technical equipment and improved personal protection.

Association of breast cancer and cytokine gene polymorphism in Turkish women.

OBJECTIVE: To investigate the association of cytokine gene polymorphism with the development of breast cancer. METHODS: The study was carried out in Uludag University Medical School, Bursa, Turkey. The study included 38 patients with breast cancer admitted to the Medical Oncology outpatient clinic, and 24 healthy controls, age and sex matched, from the Internal Medicine Department between 2004 and 2005. All genotyping of tumor necrosis factor-alpha (TNF-alpha), tumor growth factor-beta1 (TGF-beta1), interleukin (IL)-10, IL-6, and interferon-gamma (IFN-gamma) experiments were performed using polymerase chain reaction sequence-specific primers. RESULTS: The frequencies of IL-6-174GC genotype and IL-10 (-1082, -819, -592) GCC/ATA haplotype were significantly higher in the patient group (p=0.0008) when compared with controls (p=0.020). Significantly lower frequencies of IL-10 (-1082, -819, -592) ACC/ATA haplotype were observed in the patient group in comparison to the controls (p=0.026). The distribution of IFN-gamma +874, TNF-alpha 308, and TGF-beta1 codon 10-25 genotypes failed to show any statistical significant association with the development of breast cancer. CONCLUSION: Our data suggest that IL-10 (-1082, -819, -592) GCC/ATA haplotype and IL-6-174 GC genotype seem to be potential risk factors for the development of breast cancer. The presence of IL-10ACC/ATA haplotype may be protective for the oncogenesis of breast cancer.

Fatal ischemic bowel necrosis possibly due to docetaxel and cisplatin in a patient with non-small cell lung cancer.

We would like to report fatal ischemic bowel necrosis (IBN) as an unexpected complication of docetaxel and cisplatin in a patient with non-small cell lung cancer.

Efficacy of lower dose capecitabine in patients with metastatic breast cancer and factors influencing therapeutic response and outcome.

OBJECTIVE: Capecitabine exerts considerable therapeutic efficacy in metastatic breast cancer (MBC) patients previously treated with anthracyclines and taxanes. MATERIALS AND METHODS: In this study, the efficacy and safety of lower dose capecitabine (2000 mg/m(2)/d) in patients with anthracycline- and taxane-pretreated MBC were studied with a special emphasis on the potential predictors of time to tumor progression (TTP) and response to the capecitabine treatment. RESULTS: The overall response rate (ORR) was 17%. The median TTP was 5 months. Among various factors analyzed, univariate analysis showed that a performance status (PS) of 2 and the presence of visceral metastases were inversely correlated with TTP. Multivariate analysis showed that a poor PS score was associated with impaired TTP. CONCLUSIONS: Our study indicates that lower dose capecitabine has substantial antitumor activity and a favorable safety profile in the treatment of anthracycline- and taxane-pretreated MBC. Also, only performance score was demonstrated to be a significant parameter affecting TTP.

Response to neoadjuvant chemotherapy in breast cancer could be predictable by measuring a novel serum apoptosis product, caspase-cleaved cytokeratin 18: a prospective pilot study.

The M30-monoclonal antibody recognizes a neo-epitope of cytokeratin 18 which is formed after caspase-cleavage during apoptosis. Caspase-cleaved cytokeratin 18 is released from apoptotic cells into circulation. The aim of this study was to evaluate the relationship between M30-antigen level and chemotherapy response in neoadjuvant treatment of breast cancer. Forty-two patients with invasive breast carcinoma received 4 cycles of anthracycline based neoadjuvant chemotherapy. Serum samples were obtained for assessment of M30-antigen levels before the administration of first chemotherapy cycle (baseline), and then after 24 and 48 hours for determination of chemotherapy induced apoptosis. M30-antigen levels at 24 and 48 hours were found to be significantly higher than baseline (p < 0.001, p = 0.003, respectively). M30-antigen levels in responders showed statistically significant increases at 24 and 48 hours (p < 0.001; p = 0.004, respectively), while statistically significant increases were not observed in nonresponders. Percentage change of M30-antigen levels was significantly higher in responders than nonresponders at 24 hours (p = 0.020). In conclusion, our study revealed a significant relationship between increases of M30-antigen levels in serum and overall response to therapy.

Phase II study of induction chemotherapy with gemcitabine plus 5-fluorouracil followed by gemcitabine-based concurrent chemoradiotherapy for unresectable locally advanced pancreatic cancer.

AIMS AND BACKGROUND: To evaluate the efficacy and tolerability of a new treatment approach including induction chemotherapy (CT) and concurrent chemoradiotherapy (CRT) in unresectable, locally advanced pancreatic cancer (LAPC). PATIENTS AND METHODS: Twenty-four patients with LAPC were enrolled in the study. They first received induction CT consisting of 5-fluorouracil (5FU) (500 mg/m2) and gemcitabine (1000 mg/m2), which were given weekly for 3 weeks of every 4. Patients showing a response or disease stabilization after 2 cycles of induction CT received CRT consisting of external beam radiotherapy (50.4-54 Gy in fractions of 1.8 Gy/day) and gemcitabine (350 mg/m2, weekly for 6 weeks). Patients without disease progression received 2 additional cycles of CT consisting of 5FU plus gemcitabine with the same doses and schedule as given in the induction CT. RESULTS: After the end of the study, 2 (8%) and 5 (21%) patients showed complete and partial responses, respectively. Five patients (21%) had disease stabilization. The grade 3 and 4 toxicities associated with CT were neutropenia (21%) and thrombocytopenia (4%). The grade 3 and 4 toxicities occurring in patients who received CRT were neutropenia (24%), thrombocytopenia (24%), diarrhea (18%), and nausea (12%). The median progression-free survival for all patients was 6 months (95% CI, 3.6-8.4), and the median overall survival was 11 months (95% CI, 8.16-13.84). CONCLUSIONS: The CRT approach of this study is moderately active and has an acceptable toxicity profile. However, the incorporation of combination CT into CRT at the present schedule could not produce any additional benefit over CRT alone. Newer agents with more systemic activity are clearly warranted.

Phase II study of gemcitabine plus paclitaxel in metastatic breast cancer patients with prior anthracycline exposure.

UNLABELLED: Chemotherapy provides palliation and modest prolongation of symptom-free survival in metastatic breast cancer. Taxane containing regimens are commonly considered to be among the initials in metastatic setting due to earlier use of anthracyclines in the course of breast cancer. Therefore, we conducted this Phase II study to assess efficacy and safety of gemcitabine plus paclitaxel (GT) combination therapy in anthracycline pretreated metastatic first-line setting. PATIENTS AND METHODS: The study enrolled 26 women with pathologically confirmed and measurable metastatic breast cancer who were previously treated with anthracycline but no prior chemotherapy for metastatic disease. Twenty six and twenty four patients were eligible for toxicity and efficacy evaluations respectively. Mean age was 47.3 years and median ECOG performance status was 0. Twenty patients (76.9 percent) had visceral metastases, most commonly located in liver and lung. Treatment schedule was as follows: paclitaxel 175 mg/m2 was administered intravenously in 3 hours on Day 1 and gemcitabine 1000 mg/m2 was administered intravenously in 30 minutes on Day 1 after paclitaxel application, and on Day 8 every 21 days. RESULTS: Objective response rate was 41.7 percent (95 percent CI: 21.9-61.4) with 16.7 percent (95 percent CI: 1.7-31.6 percent) CR, and 25.0 percent (95 percent CI: 7.6-42.3 percent) PR. Median time to progression and overall survival were 9.6 and 14.5 months, respectively. Grade 3-4 toxicity was observed in 34.6 percent (9) patients. Treatment of two patients was discontinued due to toxicity, consisting of Grade 3 hypersensitivity reactions and Grade 4 infections in one patient each. Dose reductions due to myelotoxicity were performed in 4 (15.3 percent) patients. Hematologic toxicities were generally manageable with appropriate dose modifications and supportive care. CONCLUSION: Gemcitabine and paclitaxel combination regimen is effective and has manageable toxicity profile as first line metastatic setting.

Splenic hemangiopericytoma and serosal cavernous hemangiomatosis of the adjacent colon.

A healthy 31-years-old man presented with a three-year history of abdominal discomfort. Radiological examinations revealed multifocal tumoral lesions in the spleen. The patient underwent splenectomy for differential diagnosis and treatment. During the operation, in addition to the splenic masses, there were also multiple millimetric purpuric-like lesions on the colonic serosal surfaces adjacent to the splenic hilus. One of them was excised. Histologic examination showed hemangiopericytoma of the spleen and cavernous hemangioma of the adjacent colon. This is the first report showing the close association of these two distinct lesions with vascular origin in the literature. Despite not having any apparent evidence, there may be a sequential relationship between the hemangiopericytoma of the spleen and cavernous hemangiomas.

Relation between insulin resistance and serum concentrations of IL-6 and TNF-alpha in overweight or obese women with early stage breast cancer.

Insulin resistance (IR) and obesity may be risk factors for breast cancer. The mechanism of IR in patients with cancer has not been fully clarified yet. This study was conducted to evaluate the possible role of circulating cytokines; tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) in inducing IR in 20 overweight or obese patients with early stage breast cancer and to compare their levels with that of body mass index matched 20 healthy controls. IR was calculated by homeostasis model assessment (HOMA) method. Four groups were formed according to a 2.7 HOMA-IR cut-off value as breast cancer with or without IR and controls with or without IR. IL-6 and HOMA-IR values were found to be higher in breast cancer patients with IR compared to other groups. There was no significant difference in TNF-alpha levels between groups. HOMA-IR values correlated with estradiol and IL-6 levels in all breast cancer patients but not TNF-alpha. HOMA-IR values, serum insulin, estradiol and IL-6 levels in the receptor positive group were significantly higher than those of the receptor negative group. These results suggested a possible contribution of endogenous IL-6 production and hyperinsulinemia to the development of breast cancer in overweight or obese patients with prominent IR.

Comparison of clinical outcomes of different erythropoietin usage strategies.

AIM: There is no comprehensive study that compares the different usage strategies of recombinant human erythropoietin (rHuEPO) in platinum-induced anemia. In order to clarify this issue, we conducted a prospective clinical study. MATERIAL AND METHODS: Seventy-seven patients were studied in three main groups. Group 1 (n = 17) consisted of cancer patients without anemia. These patients received rHuEPO starting from the first chemotherapy cycle. Group 2 (n = 26) consisted of patients whose hemoglobin (Hb) values decreased by at least 1 g/dL after the first cycle of chemotherapy. Group 3 (n = 34) consisted of patients whose Hb values dropped below 10.5 g/dL after the second chemotherapy cycle. Groups 2 and 3 were each divided into two subgroups. In groups 1, 2A and 3A rHuEPO (5000 U/day subcutaneously three times a week) treatment was continued until three weeks after the completion of chemotherapy. In groups 2B and 3B, rHuEPO was given for 12 weeks only. RESULTS: There were no prominent differences between the Hb values of these groups throughout the chemotherapy cycles. Transfusion rates and the number of patients who became anemic were also not different between groups. CONCLUSION: No rHuEPO usage strategies are superior to others in terms of Hb levels and transfusion requirements. The decision as to when rHuEPO is to be added to platinum-containing therapy should be tailored to the health conditions of individual patients.