Adjuvant chemotherapy with cisplatin, etoposide, fluorouracil and leucovorin for gastric carcinoma.

PURPOSE: The aim of this study was to evaluate the efficacy of cisplatin, etoposide, 5-fluorouracil (5-FU), and leucovorin (L; CEFL) combination chemotherapy given as adjuvant treatment to patients with stage III gastric cancer. PATIENTS AND METHODS: A total of 33 patients who had undergone curative resection for stage III gastric adenocarcinoma were enrolled in our adjuvant chemotherapy protocol to receive 6 cycles of CEFL starting within 8 weeks from surgery. CEFL consisted of cisplatin 30 mg/m2 on days 1-3; 5-FU 300 mg/m2 continuous infusion on days 1-3; and etoposide 90 mg/m2 on days 1-3. Cycles were repeated every 4 weeks. Relapse-free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meier method. Comparison between groups was carried out using log-rank test. RESULTS: Treatment was completed by 30 (91%) patients. After a mean follow-up of 31 months 15 (50%) patients have relapsed. Mean RFS was 31 months (range 6 to 114+). Patients with stage IIIA disease had longer RFS that those with stage IIIB (37 vs. 25 months, p>0.05). Mean OS was 35 months (range 4 to 114+), while stage IIIA patients survived longer than IIIB ones (42 vs. 27 months, p>0.05). Principal side effects of therapy were from the bone marrow and the gastrointestinal tract. There were 2 treatment-related deaths due to neutropenic sepsis. CONCLUSION: CEFL regimen appears to be an effective adjuvant treatment for patients with stage III gastric carcinoma as it prolongs both RFS and OS. However, its pronounced myelotoxicity requires the prophylactic use of granulocyte colony stimulating factor (G-CSF).

Second line chemotherapy with methotrexate and gemcitabine in patients with relapsing head and neck cancer.

PURPOSE: The aim of this study was to evaluate the efficacy and toxicity profile of the combination of methotrexate and gemcitabine given as second-line treatment in patients with relapsing and/or metastatic head and neck cancer (HNC). PATIENTS AND METHODS: A total of 21 patients with HNC who had relapsed after first-line treatment with cisplatin-containing regimens were enrolles. Treatment consisted of intravenous (i.v.) administration of methotrexate 30 mg/m(2) and gemcitabine 800 mg/m(2) on days 1, 8, and 15 in cycles of 28 days. Primary sites included the larynx, tongue, nasopharynx, hypopharynx, nasal cavity, and parotid gland. The study end point was the evaluation of treatment efficacy and toxicity. RESULTS: Seven (33%) patients received only 1 or 2 cycles and discontinued treatment because of disease progression. Among 14 patients evaluable for respone, 1 complete (CR) and 2 partial responses (PR) were observed, yielding a response rate of 21.4%. The patient with CR remains relapse-free for 74(+) months. The 2 PR patients relapsed after 14 and 25 months and are still alive at 18 and 32 months, respectively. Seven patients showed minor response (MR) or stable disease (SD) with symptomatic relief lasting 4-12 months (mean 8). All but 2 of adequately treated patients (12/14 or 85.7%) attained a clinical benefit response (CBR). Mean time to progression (TTP) of all patients was 8 months (range 1-74(+)), while mean overall survival (OS) was 14 months (range 1-74(+)). Toxicity was mild to moderate and easily manageable. CONCLUSION: Methotrexate and gemcitabine combination is an effective second-line treatment for patients with relapsing and/or metastatic HNC. Moreover, this regimen is well tolerated with mild to moderate, easy to treat, toxicity.

Correlation of tissue transglutaminase expression on breast cancer tissue with time to relapse, overall survival, and clinical and molecular prognostic factors: a preliminary report.

PURPOSE: To correlate tissue transglutaminase (TTG) expression with the expression of molecules with prognostic significance in breast cancer patients and with classical clinical parameters (disease stage, histological grade, overall survival (OS), relapse rate, disease progression and time to treatment failure-TTF). PATIENTS AND METHODS: Paraffin-embedded tissue specimens from 68 breast cancer patients were studied retrospectively for TTG expression, estrogen (ER) and progesterone (PG) receptors, c-erbB-2, p53, Bcl-2, and Ki-67. Sixty-seven patients were females (mean age 60.5 years). Histology was ductal carcinoma in 53 (inflammatory in 2 and mucinous in 1 of them), lobular in 13 and tubular in 2 cases. Grade was 1 and 2 in 45 cases and 3 in 23. Forty-six patients had early-stage disease (I - IIB) and 22 advanced (IIIA - IV). RESULTS: Fifty patients had at least 1 favorable molecular prognostic factor while all but 3 had at least 1 unfavorable prognostic factor. Twenty-nine (42.6%) patients have relapsed so far (mean TTF 31.4 months). Fifty-two (76.5%) patients are still alive (mean OS 38.5 months). Of the 59 patients with nodal and/or metastatic disease 54 were expressing TTG and 32 Bcl-2. Five were not expressing either one while 22 were expressing both. Of the 9 patients without nodal and/or metastatic disease all but one were expressing TTG and Bcl-2. Analyzing these subgroups of patients there was sufficient evidence that TTG expression was correlated with a trend for prolonged survival both in patients with localized and extensive disease, while the coexpression with Bcl-2 was correlated with a trend for prolongation of TTF and OS, both in relapsing and nonrelapsing patients. However, these differences did not reach statistical significance. Similar comparisons of TTG expression with the presence of adverse prognostic factors verified a beneficial effect of TTG expression on OS in all subgroups. CONCLUSION: Our data suggest that TTG is an independent favorable prognostic factor for survival, possibly enhancing the apoptotic effect of chemotherapy.

Front-line treatment of metastatic breast cancer with docetaxel and epirubicin: a multicenter dose-escalation study. The Greek Breast Cancer Cooperative Group (GBCCG).

PURPOSE: To determine the maximum tolerable dose (MTD) and the dose-limiting toxicity (DLT) of docetaxel (D) in combination with epirubicin (Epi) in patients with advanced breast cancer. PATIENTS AND METHODS: Forty-seven chemotherapy-naïve metastatic breast cancer patients aged < 75 years with PS (WHO) 0-2 and adequate bone marrow, renal, liver and cardiac function, were enrolled in the study. Epi was given as a five-min bolus i.v. infusion on day 1 (d1) in escalated doses with increments of 10 mg/m2; D was given in a one-hour infusion after appropriate premedication on either day 1 or on day 2 in escalated doses with increments of 10 mg/m2. The patients' median age was 60 years, 42 (89%) had a PS (WHO) 0-1, 16 (34%) were premenopausal and 25 (53%) had visceral disease. RESULTS: When the two drugs were given on the same day, the MTD1 was reached at the doses of Epi 60 mg/m2 and D 80 mg/m2; administration of G-CSF could not result in a dose intensification. When the drugs were given on two consecutive days, the MTD2 was reached at the doses of Epi 80 mg/m2 (d1) and D 90 mg/m2 (d2). The dose-limiting events were febrile neutropenia and grade 4 neutropenia, which developed in 30 (64%) patients during the study; among 227 delivered cycles grade 3-4 neutropenia occurred in 64 (28%) cycles but only 22 (10%) of them were complicated by fever. There were no septic deaths. Grade 1-2 neurosensory toxicity occurred in nine (19%) patients, mild edema in eight (17%) and allergic reactions in five (11%). Four (9%) patients presented a greater than 10% decrease of LVEF and treatment discontinuation was required in two of them; none of the patients developed congestive heart failure. Nevertheless, one patient suddenly died 10 days after treatment initiation of myocardial ischemia, and this death is considered treatment-related. Five (14.7%) complete and thirteen (38.2%) partial responses (ORR: 53.9%; 95% confidence interval: 36.1%-69.7%) were observed in 34 evaluable patients. Ten (29.4%) and six (17.6%) patients had stable and progressive disease, respectively. The median duration of response and time to tumor progression were five and seven months, respectively. The median survival has not yet been reached. CONCLUSIONS: The combination of epirubicin and docetaxel is a feasible and well tolerated regimen, but the MTD depends on the administration schedule of the drugs.