Impact of hyperlipidaemia on the orbital bone cefotaxime levels in rats.

Facial injuries are critical conditions, leading to serious complications, such as occult facial infections. Infectious endophthalmitis occurs despite of antibiotics use during implantation of intraocular lenses and is generally resistant to antibiotic therapy. It is a crucial situation in ophthalmology, since it often induces a substantial reduction of visual acuity and in some cases the loss of the eye despite treatment. It is, therefore, important to obtain drug levels able to exert antimicrobial effect in the diseased organ. The distribution of a drug depends on the binding extent to both plasma proteins and tissues and only the free drug is capable to be transported/diffused across membranes from blood vessels into tissues, in order to achieve its effect on the target organ. Hyperlipidaemia and consequent enhanced concentration of free fatty acid can modify binding pharmacokinetics of antibiotics through antagonism for the same binding sites. Cefotaxime, the third generation cephalosporin with easy penetration in a variety of tissues and body fluids and low incidence of adverse effects, can obtain adequate concentration in blood, eye bulb, and in the orbital bones. Its levels are influenced by hyperlipidaemia with clinical impact.

Anticoagulant-induced changes on antibiotic concentrations in the serum and bones.

The aim of this study was to determine whether the co-administration of acenocoumarin as anticoagulant and certain quinolones, i.e., cefapirin, pefloxacin and ciprofloxacin increased the levels of the given antibiotics and whether this resulted in a prolongation of prothrombin time. Seventy male albino Wistar rats aged 8-10 weeks and weighed 170 +/- 14 g were used and divided into seven groups (I, II, III, IV, V, VI, VII: n=10). The rats in group I received cefapirin via 1 g/kg/8h im injection. Group II received cefapirin via of 1 g/kg/8h im injection and 0.1 mg/kg/24h p.o. acenocoumarin. Group III received ciprofloxacin 0.18 mg/kg/24h im. Group IV received ciprofloxacin 0.18 mg/kg/24h im and 0.1 mg/kg/24h p.o. acenocoumarin. Group V received 10 mg/kg/24h pefloxacin im. Group VI received 10 mg/kg/24h pefloxacin im and 0.1 mg/kg/24h p.o. acenocoumarin while Group VII received only acenocoumarin 0.1 mg/kg/24h p.o. Drug administration was performed over a total of 5 doses in order to obtain steady state concentrations in the plasma and tissues. The animals were sacrificed by decapitation 2 h after the last antibiotic administration. Prothrombin time and antibiotic concentrations in the serum, femur and mandible were assessed. In the study, all the antibiotics were found to prolong prothrombine time following acenocoumarin administration. In addition, perfloxacin and ciproflaxin concentrations were increased in the serum and mandible after acenocoumarin treatment. Cepafirin levels remained unaffected after the administration of this anticoagulant. In conclusion, anticoagulant and quinolone co-administration led to significant pharmacokinetic interactions. Thus particular attention should be paid in the case of these drugs being used in combination in clinical practice.

Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial.

The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German-speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial compared bortezomib (BTZ) before and after high-dose melphalan and autologous stem cell transplantation (HDM, PAD arm) compared with classical cytotoxic agents prior and thalidomide after HDM (VAD arm) in multiple myeloma (MM) patients aged 18-65 years. Here, the long-term follow-up and data on second primary malignancies (SPM) are presented. After a median follow-up of 96 months, progression-free survival (censored at allogeneic transplantation, PFS) remained significantly prolonged in the PAD versus VAD arm (hazard ratio (HR)=0.76, 95% confidence interval (95% CI) of 0.65-0.89, P=0.001). Overall survival (OS) was similar in the PAD versus VAD arm (HR=0.89, 95% CI: 0.74-1.08, P=0.24). The incidence of SPM were similar between the two arms (7% each, P=0.73). The negative prognostic effects of the cytogenetic aberration deletion 17p13 (clone size ⩾10%) and renal impairment at baseline (serum creatinine >2 mg dl-1) on PFS and OS remained abrogated in the PAD but not VAD arm. OS from first relapse/progression was similar between the study arms (HR=1.02, P=0.85). In conclusion, the survival benefit with BTZ induction/maintenance compared with classical cytotoxic agents and thalidomide maintenance is maintained without an increased risk of SPM.

Amnemonic traces: Traumatic after-effects.

Τhis article addresses the problem of amnemonic traces. The author considers various effects that traumatic experiences can have on the psychic apparatus and, more specifically, those that give rise to situations in which nothing is remembered and nothing is repeated by the patient. She presents data from the analyses of two patients and explores whether it might be possible to give a more accurate description of factors and processes that accelerate the fading of traumatic experiences from the memory network. As somatic disturbances, or illnesses, often accompany or follow traumatic upheavals, the author examines some examples of how somatic events can be viewed as linked to traumatic turmoil and understood as channels of expression of what remains silent in the mental realm. Some suggestions concerning prerequisites for analytic work with patients who confront the analyst with ruptures and erasures in mental functioning and with reductions in mental processing are discussed. How the analyst's psychic economy is involved while working with such patients is also considered.

Comparative study of serum and synovial fluid interleukin-11 levels in patients with various arthritides.

OBJECTIVE: To determine the levels of serum and synovial fluid (SF) interleukin (IL)-11 in patients with various arthritides and estimate the contribution of IL-11 to acute phase response (APR). DESIGN AND METHODS: Serum and SF IL-11 were measured by ELISA in patients with rheumatoid arthritis (RA, n = 31), seronegative spondyloarthritis (SSA, n = 23), gout (GT, n = 14) and osteoarthritis (OA, n = 20) and were correlated with ESR and acute phase proteins as well as with cytokines IL-1 alpha, IL-1 beta, IL-6, and TNF alpha. RESULTS: IL-11 was detected in both serum and SF in each group, with IL-11 being statistically higher in SF than serum in all groups, suggesting reduced catabolism or increased synthesis of IL-11 intra-articularly. Median SF IL-11 levels were higher in OA patients than in other groups and in the treated than in the untreated RA subgroup. Moreover, serum and SF IL-11 were correlated significantly with each other, and moderately with the other cytokines examined in RA, SSA, and GT, but not in OA patients, while a significant negative correlation was found with a few of the inflammatory markers examined in each group. CONCLUSIONS: Our findings provide evidence of extensive intra-articular expression of IL-11 in arthritides, especially in OA and treated RA patients, suggesting a protective role for IL-11 in joints, probably through the induction of tissue inhibitor of metalloproteinases.

Quinolone levels in serum and maxillofacial tissues under ibuprofen co-administration following surgical trauma.

Administration of antibiotics is considered to be an important factor, during or after operational procedures in the maxillofacial area, in order to avoid post-surgical complications. Furthermore, administration of anti-inflammatory drugs is often prescribed for control of the post-operative pain. The aim of this study was to determine the levels of quinolones in serum and tissues (parotid gland, tongue, mandible), during traumatic injury in the oral cavity, with or without co-administration of ibuprofen, a non-steroidal anti-inflammatory drug. Four groups of Wistar rats, (A, B control), (C, D experimental) were used. In the experimental group, traumatic injury was performed through the whole length of the cheek. Groups B and D received ibuprofen. The quinolone levels in serum and tissues were estimated by the inhibition zone of B. subtilis. Free fatty acid (FFA) levels and the adrenal weight, considered as a stress index, were increased in trauma groups. Quinolone concentrations in serum and in most of the tissues were significantly higher in the experimental groups compared to the controls. However, the co-administration of ibuprofen caused a higher increase of the quinolone levels in the control animals than in the experimental groups.

Stress-induced lidocaine modification in serum and tissues.

The aim of this study is to examine the influence of acute (trauma) and chronic (cold swimming and adjuvant rheumatoid arthritis) stress on lidocaine concentrations in plasma. Forty male Wistar rats were used. The animals were divided into four groups. Group A served as control. Group B underwent mandible osteotomy. Group C was submitted to swimming stress in cold water 4 degrees C for ten minutes daily for 15 minutes, while group D underwent experimental arthritis with Freud's adjuvant. All groups received lidocaine i.m (2.5 mg/kg). Blood samples were collected and FFA (free fatty acid), unbound-lidocaine, albumin and a1-acid glycoprotein concentrations were estimated. Furthermore, the adrenals, heart and liver were isolated. The adrenals' relative weight (adrenal weight/body weight) was assessed, while lidocaine concentrations in the heart and the liver incubation medium were measured by intertechnic a-counter. Lidocaine and FFA levels in serum as well as the adrenal weights demonstrated a significant elevation in stress-groups as compared to the control group. Furthermore, in the stress-groups, lidocaine concentrations in heart tissue were significantly increased, whereas in the liver they were significantly reduced as compared to the control group. Our results indicate that stress can alter lidocaine levels in plasma and tissues, suggesting that stress should be considered an important factor when determining the dosage of lidocaine in clinical application.

Light induced changes in quinolone levels in rat serum and tissues.

Circadian rhythm may induce alterations of the pharmacokinetic properties of several drugs in clinical use. The aim of the study was to investigate whether lighting conditions alter the quinolone (pefloxacin) levels in serum and tissues and to determine any accumulation of the drug in the skin. Thirty male Wistar rats were divided into groups A, B, C, (n=10). The animals of group A were housed under 12h light/12h dark conditions, group B under 24h UV and group C was kept in complete darkness. All animals received 5 doses of 11mg/Kg pefloxacin every 8h for 48h.Pefloxacin levels were determined in serum, skin and femur by the inhibition zone in E.coli. in vitro. Pefloxacin concentrations in serum were increased in 24h darkness living status and decreased in 24h UV conditions as compared to group A animals. Additionally, both skin and femur pefloxacin levels were decreased under dark and UV conditions. In conclusion total light as well as total dark exposure may lead to pefloxacin pharmacokinetic changes which may have implications in the effectiveness of the drug in tissues.

Methotrexate, etoposide, ifosfamide and cisplatin (MVIP): An effective salvage therapy for patients with refractory or relapsed germ-cell tumors.

PURPOSE: To study the efficacy and toxicity of a combination of methotrexate, etoposide, ifosfamide and cisplatin (MVIP) in patients with germ-cell tumors (GCTs) refractory to or relapsed after first-line platinum-based chemotherapy. PATIENTS AND METHODS: Between 1989 and 2001 22 male patients with GCTs refractory (n=7) or relapsed (n=15) after first-line platinum-based chemotherapy entered prospectively the study. Their median age was 29 years. Methotrexate 250 mg/m(2) as 4-hour infusion plus folinic acid were administered on day 1. On day 3 cisplatin 100 mg/m(2) with pre and posthydration was given as 30-min infusion; and ifosfamide 5 g/m(2) with mesna as 24-hour infusion. Etoposide 100 mg/m(2)/day as 1-hour infusion was administered on days 3-5. Cycles were repeated every 3 weeks. Granulocyte colony stimulating factor (GCSF) was administered either therapeutically (grade 3-4 neutropenia-/+antibiotics) or prophylactically (nadir grade 3-4 neutropenia in the previous chemotherapy cycle). RESULTS: All patients were evaluable for response, toxicity and survival. A total of 95 cycles (median 4 cycles per patient) of MVIP were administered. Fourteen (63.6%) patient achieved complete response (CR), and 8 (36.4%) were treatment failures. Long-term disease-free survival (DFS) with MVIP was achieved in 11 out of 14 (78.6%) CR patients or 50% of all patients. After a median follow-up period of 55.04(+) months (range 4-147(+) months) overall survival is 59.09%. Good performance status (PS) was the only significant predictor for survival. Toxicity was easily manageable with no deaths or therapy delays. CONCLUSION: MVIP conventional chemotherapy proved particularly effective in terms of CR rate, overall survival and long-term DFS in this very poor prognosis patient population. Toxicity was tolerable. The results obtained are equal or even superior compared with those taken by more intensive regimens, including high-dose chemotherapy. MVIP justifies further studies in patients with refractory/ relapsed GCTs.

Methotrexate, etoposide, ifosfamide and cisplatin (MVIP): an effective first-line therapy for IGCCC intermediate / poor prognosis patients with germ-cell tumors. Single institution experience.

PURPOSE: To evaluate the antitumor activity and toxicity of methotrexate (M), etoposide (V), ifosfamide (I) and cisplatin (P) combination chemotherapy (MVIP) administered to chemotherapy-naive patients with intermediate / poor prognosis germ-cell tumors (GCT) according to the International Germ Cell Cancer Collaborative Group (IGCCCG) consensus classification system (IGCCC). PATIENTS AND METHODS: From 1992 to 2001 24 consecutive intermediate (n=14)/poor prognosis (n=10) GCT male patients entered prospectively this phase II trial. Patients received methotrexate 250 mg/m(2), day 1, with folinic acid rescue; cisplatin 100 mg/m(2) with appropriate hydration, day 3; ifosfamide 5 g/m(2) with mesna uroprotection, day 3; and etoposide 100 mg/m(2)/day, days 3-5. MVIP was repeated every 3 weeks. RESULTS: After 120 cycles of MVIP (median 5, range 2- 7) 18 (75%) patients achieved complete remission (CR). CR was attained by 12 out of 14 (86%) intermediate prognosis and 6 out of 10 (60%) poor prognosis patients. Three CR patients (2 intermediate, 1 poor prognosis) of out 18 (16.7%) relapsed after a median of 6 months and 1 of them (poor prognosis) achieved a durable CR with second-line chemotherapy. After a median follow-up of 37 months (range 5-115 months) 16 patients (10, 71% intermediate and 6, 60% poor prognosis) are long-term survivors with no evidence of disease (NED), and 2 (one of each group) are alive with disease. Actuarial overall survival at 3 and more years is 75% and NED survival is 67%. Hematologic toxicity was most common and easily manageable (grade 3-4 neutropenia 46% of the cycles and thrombocytopenia 25% of the cycles). There were no deaths, withdrawals or delays in chemotherapy administration because of toxicity. CONCLUSION: MVIP conventional chemotherapy proved very effective in terms of CR rate, overall survival and longterm NED survival in these unfavorable groups of GCT patients. The results obtained are encouraging and compare favorably with those taken by more intensive regimens including high-dose chemotherapy. We believe that MVIP justifies further studies.

Phase I study of postoperative radiotherapy with concomitant weekly irinotecan, 5- fluorouracil and folinic acid in locally advanced rectal cancer.

PURPOSE: 5- fluorouracil (5-FU)-based chemotherapy with concomitant pelvic radiotherapy represents the gold standard of the adjuvant treatment of high-risk rectal cancer. This study aimed to determine the maximum tolerated dose (MTD) of weekly irinotecan (CPT-11) when combined with fixed 5FU/FA doses and pelvic irradiation. PATIENTS AND METHODS: Twenty- four patients with stage II or III rectal cancer were accrued. All had undergone curative surgery before entering the study. Standard pelvic radiotherapy was delivered (50.4 Gy, 1.8 Gy/ fraction in 5.5 weeks). The 5-FU/FA doses were 350/250 (mg/m(2)) in the first 6 patients and 250/100 in the remaining patients. Weekly doses of CPT-11 started at 30 mg/m(2) with escalation steps of 10 mg/m(2). CPT-11 was escalated when 3 patients had been monitored for 8 weeks, without a dose limiting toxicity (DLT). RESULTS: Twenty-three out of 24 patients completed the chemoradiation course. Only 1 patient discontinued the treatment due to persistent grade 3 diarrhea. Of the 144 planned weekly chemotherapy cycles, only 7 were omitted as a result of persisting grade 2-3 gastrointestinal toxicity in 3 patients and grade 3 neutropenia in 1 patient. Grade 3 gastrointestinal DLTs were observed at doses at the level of 30/250/100 in 1 patient and 70/250/100 in 2 patients. Late DLTs were severe radiation dermatitis and colitis at 40/ 350/250 (1 patient) and 70/250/100 (2 patients), respectively. With a follow-up of 18 months 20 (83.3%) patients remain disease- free. CONCLUSION: The administration of weekly CPT-11/ 5FU/FA with concomitant pelvic radiotherapy is feasible and effective. This treatment schedule is associated with mild myelosuppression and mild to moderate gastrointestinal toxicity. Caution should be paid on late radiotherapy-induced toxicities. The MTD of weekly CPT-11 is 30 mg/m(2) when combined with 5FU/FA doses (mg/m(2)) of 350sol;250 and reaches 60 mgsol;m(2) with lower doses of 5FU/FA (250/100).

The RACOX phase I study: radiation (RA), capecitabine (C) and oxaliplatin (OX) as adjuvant treatment of stage II and III rectal cancer.

PURPOSE: The aim of this phase I trial was to deter- mine the maximum tolerated dose (MTD) of adjuvant che- motherapy (CT) with oxaliplatin in combination with capecitabine during concomitant pelvic radiotherapy (RT) in patients with rectal cancer. PATIENTS AND METHODS: Eligible patients had pathological stage II (T3-4N0M0) or III (any T N1-2M0) rectal adenocarcinoma, and no prior treatment other than curative resection. Fixed capecitabine dose (825 mg/m(2) bid on days 1-14 and 22-35) was given and external beam RT was delivered to the pelvis (50.4 Gy in 27 fractions in 5.5 weeks, with field reduction after 45 Gy in linear accelerator, 18Mev). Oxaliplatin was tested at 4 dose levels: 100, 110, 120 and 130 mg/m(2). The dose of oxaliplatin was escalated when all 3 entered patients at each level had been monitored for at least 8 weeks after the CT/RT course without dose limiting toxicities (DLTs). In the presence of a DLT at any dose level, a further 3 patients were enrolled. If only 1 of the 6 patients experienced a DLT, escalation could proceed. The MTD was defined as the level at which >/= 2 of 3 to 6 patients experienced DLTs. Fifteen patients (10 males and 5 females, median age 62 years) were enrolled at oxaliplatin dose levels of 100 (n=3), 110 (n=3), 120 (n=3) and 130 mg/m(2) (n=6). RESULTS: All patients completed the planned CT/RT course. Dose reduction or delay of the 2nd CT cycle was not required. No DLTs were observed at all dose levels. Overall, gastrointestinal and neurological toxicities were mild and transient. Toxicities included non-dose-limiting nausea / vomiting, diarrhea, dysesthesias in 2 level III and in 1 level IV patients. Grade II myelotoxicity, mainly neutropenia, was seen in 6 patients. With a median follow-up of 4 months (range 2-12) after the completion of CT/RT, late toxicities were restricted to grade II radiation colitis and dermatitis in 2 and 2 patients, respectively. CONCLUSION: The combination of pelvic RT, capecitabine and 3-weekly oxaliplatin is feasible and well tolerated. The MTD was not reached up to the dose of 130 mg/m(2) of oxaliplatin, which is the recommended dose.

Intraoperative electron beam radiotherapy followed by moderate doses of external beam radiotherapy in the treatment of resected soft tissue sarcomas of the extremities.

PURPOSE: Soft tissue sarcomas (STS) have a high incidence of local recurrence. In an effort to improve the local control rate and the survival in patients with STS, treatment strategies employing intraoperative electron beam radiotherapy (IOERT) in combination with external beam radiotherapy (EBRT) and extensive surgical resection have been explored. This study assesses the rate of overall survival (OS), local control and toxicity of this multimodal approach for primary and recurrent STS of the extremities. PATIENTS AND METHODS: From 1999 to 2004, 36 patients were treated at Agios Savvas Cancer Hospital for primary or recurrent extremity STS with IOERT as a component of their treatment. All patients underwent surgical resection, IOERT, and most of them received postoperative EBRT with a median dose of 45 Gy. Chemotherapy was given to patients with high grade tumors. Thirteen patients were treated for primary disease and 23 for isolated local recurrence.The locations of the tumors were as follows: upper limbs n=19, lower limbs n=17. Tumor size was >5 cm in 16 (44%) patients and high-grade histology (II-III) was present in 24 (67%) patients. Six (17%) patients had positive surgical margins. RESULTS: With a median follow up of 24 months (range 6-48) OS was 72% (84.5% for patients with low grade lesions compared to 65% for high grade lesions, p=0.127, and 90% for tumors <5 cm compared to 50% for tumors >5 cm, p=0.0136). Overall local tumor control rate was 89% (92% in primary disease group versus 87% in isolated local recurrence group, p=0.136, and 93% for patients with negative surgical margins versus 67% for those with positive margins, p=0.0013). Distant metastases occurred in 10 patients (1 of 13 (8%) with primary disease, and 9 of 23 (39%) with isolated local recurrence). All distant metastases were to the lungs. Twelve (33%) patients developed moderate neurotoxicity. CONCLUSION: In selected patients, IOERT results in excellent local control and OS with acceptable toxicity.

Somatization and dream work.

This paper refers to somatization processes which correspond to organic disorders in the body or illness. In relation to it, the author discusses dream production and its development as major indicators to be used in following the course of treatment, as changes, both positive and negative, are reflected in the form, texture, and content of dreams. These points are illustrated by clinical material.

Biocompatibility of resin composites subcutaneously implanted in rats with experimentally induced arthritis.

OBJECTIVE: To evaluate the biocompatibility of resin composite specimens with different curing efficiency, subcutaneously implanted in rats with experimentally induced arthritis. METHODS: The amount of remaining CC bonds (%RDB) of hybrid resin composite specimens photopolymerized for 10s and 40s exposure time (n=3) was measured by micro-attenuated total reflectance Fourier transform infrared spectroscopy. Male Wistar rats (n=36) were classified in two groups (n=18) of healthy animals and of animals with experimentally induced arthritis. Resin composite specimens irradiated for 10s and 40s and calcium hydroxide control specimens were implanted subcutaneously in each animals' dorsum. Following 2-, 4- and 9-week periods the animals were sacrificed. The development of arthritis was defined by biochemical analysis and the changes in the relative weight of animals' organs (spleen, thymus, adrenals). Tissue reactions were examined histologically. RESULTS: %RDB per site and exposure time showed statistically significant differences. Lowest %RDB values were recorded on 40s exposed specimens. Biochemical indices and relative organ weights demonstrated statistically significant differences between healthy animals and animals with arthritis. The health status of the animals and the materials used did not influence tissue response. First and second periods of sacrifice showed reduced propensity of connective tissue development in comparison to the third period. The same applied for the second period regarding the presence of giant cells. SIGNIFICANCE: The materials tested and the animals' health status did not result in altered tissue response compared to control group. The period of sacrifice was associated with different tissue responses.

Multicenter phase II study of gemcitabine and oxaliplatin (GEMOX) as second-line chemotherapy in colorectal cancer patients pretreated with 5-fluorouracil plus irinotecan.

PURPOSE: To evaluate the efficacy and tolerance of the gemcitabine/oxaliplatin (GEMOX) combination as second-line chemotherapy for patients with advanced colorectal cancer (CRC) pretreated with an irinotecan (CPT-11)/5-fluorouracil (5-FU)/leucovorin (LV) regimen. PATIENTS AND METHODS: Patients with documented disease progression during or after first-line treatment with CPT-11 and 5-FU/LV were enrolled. Gemcitabine (1,000 mg/m(2) days 1 and 8) and oxaliplatin (100 mg/m(2) day 1) were administered every 3 weeks. RESULTS: Partial responses were observed in 6 of the 34 (17.7%) patients enrolled (intention-to-treat analysis; overall response rate: 17.7%; 95% confidence interval 4.8-30.5%). Eight (23.5%) patients experienced disease stabilization and 20 (59%) disease progression (tumor growth control rate = 41.2%). The median duration of response was 5.5 months, and the median time to tumor progression 2.7 months. The median overall survival was 9.1 months (1-year survival rate: 44.0%). Grade 3 neutropenia and thrombocytopenia occurred in 18 and 15% of the patients, respectively. Other severe non-hematologic toxicities were rare. CONCLUSION: The interesting tumor growth control rate and the favorable toxicity profile of the GEMOX regimen in pretreated patients with advanced CRC strongly suggest that this regimen may provide an alternative therapeutic option for this group of patients.

Salvage chemotherapy with gemcitabine and oxaliplatin in heavily pretreated patients with metastatic breast cancer: a multicenter phase II study.

PURPOSE: It was the aim of this study to evaluate the activity and tolerance of gemcitabine and oxaliplatin in pretreated metastatic breast cancer patients. METHODS: Thirty-one patients who had disease relapse or progression after completion of an anthracycline- and/or taxane-based front-line regimen were treated with gemcitabine 1,500 mg/m(2) on days 1 and 8 as a 30-min intravenous infusion and oxaliplatin 130 mg/m(2) on day 8 as a 4-hour intravenous infusion, in cycles of 21 days. RESULTS: Complete response occurred in 1 patient (3%) and partial response in 4 patients (13%) (overall response rate 16%; 95% confidence interval 3.2-29.1). Nine patients (29%) had stable disease and 17 (55%) progressive disease. Three partial responses (13%) were achieved among 23 patients receiving the regimen as third-line treatment. The median duration of response was 6 months (range 3-44.8), the median time to tumor progression 4.6 months (range 0.8-43.8), and the median survival 14.4 months (range 2.1-44.8). Grade 3 and 4 neutropenia occurred in 14 patients (45%), grade 3 and 4 thrombocytopenia in 6 patients (20%), and grade 2 and 3 asthenia in 4 patients (13%). There was no episode of febrile neutropenia. CONCLUSION: The gemcitabine-oxaliplatin combination is a relatively active and well-tolerated salvage regimen in patients with heavily pretreated metastatic breast cancer.