Polymorphisms of uridine glucuronosyltransferase gene and irinotecan toxicity: low dose does not protect from toxicity.

Uridine glucuronosyltransferase (UGT) gene polymorphisms have been linked to irinotecan toxicity. Our purpose was to study the association between UGT1A1*28, UGT1A7*2, and UGT1A7*3 polymorphisms and irinotecan toxicity in Greek patients receiving low-dose weekly irinotecan. Blood samples were collected for 46 patients. DNA was extracted and UGT1A1 promoter and UGT1A7 exon 1 genotyping was carried out. Laboratory tests and physical examination were performed on regular basis for the assessment of toxicity. UGT1A1*28 was significantly correlated with both haematologic and non-haematologic toxicity. Moreover, patients carrying UGT1A7 polymorphisms had significant incidence of toxicity. To conclude, UGT polymorphisms play a role in the toxicity of irinotecan, even if the drug is administered in low doses. The genotyping test may be a useful tool for the management of patients who are going to receive irinotecan.

Control of relapsed germ cell tumor and SLE nephritis by high-dose chemotherapy and autologous hematopoietic cell transplantation.

High-dose chemotherapy and hematopoietic stem cell support remains a curative treatment option for relapsed or nonresponsive germ cell tumors, and has been applied experimentally to control severe autoimmune diseases. In the present study, we report on a patient with systemic lupus erythematosus nephritis who developed a nonseminomatous germ cell tumor that relapsed after standard chemotherapy and surgery. The patient received high-dose chemotherapy supported by autologous hematopoietic cell transplantation based on its indication for relapsed germ cell tumors. Prolonged control of his relapsed germ cell tumor and systemic lupus erythematosus was attained with high-dose chemotherapy and hematopoietic stem cell support. An extensive literature review is provided alongside a detailed discussion of the aforementioned case.

Treatment of patients with metastatic renal cell carcinoma undergoing hemodialysis: case report of two patients and short literature review.

BACKGROUND: Renal cell carcinoma (RCC) may involve both kidneys. When bilateral nephrectomy is necessary renal replacement therapy is mandatory. Treating such patients with sequential therapy based on cytokines, antiangiogenic factors and mammalian target of rapamycin (mTOR) inhibitors is challenging. CASE PRESENTATION: The first case, a 50-year-old Caucasian female, underwent a radical right nephrectomy for RCC. Twelve years later she underwent a radical left nephrectomy along with total hysterectomy including bilateral salpingo-oophorectomy for RCC involving the right kidney and ovary. Hemodialysis was necessary because of bilateral nephrectomy. She relapsed with pulmonary metastases and enlarged mediastinal lymph nodes and received cytokine based therapy along with bevacizumab. Therapy was discontinued despite the partial response because of hemorrhagic gastritis. Therapy was switched to an antiangiogenic factor but the patient manifested a parietal brain hematoma and stopped therapy. Subsequently disease relapsed with malignant pleural effusion and pulmonary nodules and a mammalian target of rapamycin inhibitor was administered which was withdrawn only at patient's deteriorating performance status. The patient died of the disease 13 years after the initial diagnosis of RCC. CONCLUSION: Patients with RCC are in significant risk to manifest bilateral disease. Renal insufficiency requiring hemodialysis poses therapeutic challenges. Clinicians must be aware of the antiangiogenic factors' adverse effects, especially bleeding, that may manifest in higher frequency and more severe in this setting.

Prolonged survival after sequential multimodal treatment in metastatic renal cell carcinoma: two case reports and a review of the literature.

INTRODUCTION: In this case series and short review of the literature, we underline the impact of nephrectomy combined with sequential therapy based on cytokines, antiangiogenic factors, and mammalian target of rapamycin inhibitors along with metastasectomy on overall survival and quality of life in patients with metastatic clear cell renal carcinoma. CASE PRESENTATION: In the first of two cases reported here, a 53-year-old Caucasian man underwent a radical left nephrectomy for renal cell cancer and relapsed with a bone metastasis in his right humerus. He was treated with closed nailing and cytokine-based chemotherapy. For 5 years, the disease was stable and he had great improvement in quality of life. Subsequently, the disease relapsed in his lymph nodes, lung, and thorax soft tissue. He was then treated with antiangiogenic factors and mammalian target of rapamycin inhibitors. The disease progressed until September 2009, when he died of allergic shock during a blood transfusion, 9 years after the initial diagnosis of renal cell cancer.In the second case, a 54-year-old Caucasian man underwent a radical left nephrectomy for renal cell cancer. A year later, the disease progressed to his neck lymph nodes, and cytokine-based chemotherapy was initiated. While he was on cytokines, a solitary pulmonary nodule appeared and he underwent a metastasectomy. Nine months later, magnetic resonance imaging of his brain revealed a focal right occipitoparietal lesion, which was resected. After two years of active surveillance, the disease relapsed as a pulmonary metastasis and he was treated with an antiangiogenic factor. Further progressions presenting as enlarged axillary lymph nodes, chest soft tissue lesions, and thoracic spine bone metastases were sequentially observed. He then received a first-generation mammalian target of rapamycin inhibitor, an antiangiogenic factor, and later a second-generation mammalian target of rapamycin inhibitor and palliative radiotherapy. Ten years after the initial diagnosis of renal cell cancer, his disease is stable and he is on a third antiangiogenic factor and leads an active life. CONCLUSIONS: One multidisciplinary approach to patients with metastatic renal cell cancer combines nephrectomy, metastasectomy, and radiotherapy (when feasible) with medical therapy based on cytokines and targeted treatment employing agents inhibiting angiogenesis, other receptor tyrosine kinases, and mammalian target of rapamycin. This approach could prolong survival and improve quality of life.

Pancreatic adenocarcinoma-associated polymyositis treated with corticosteroids along with cancer specific treatment: case report.

BACKGROUND: Adenocarcinoma of the pancreas only rarely is associated with inflammatory myopathy. In this setting, polymyositis may be treated with glucocorticoids in combination with cancer specific treatment. CASE PRESENTATION: We present the case of a 52-year-old man with stage IIA pancreatic tail adenocarcinoma who underwent surgical treatment and six months into therapy with gemcitabine he developed symmetrical, painful, proximal muscle weakness with peripheral oedema. Re-evaluation with imaging modalities, muscle histology and biochemistry conferred the diagnosis of polymyositis associated with pancreatic cancer progression. The patient was treated with glucocorticoids along with gemcitabine and erlotinib which resulted in complete remission within six months. He remained in good health for a further six months on erlotinib maintenance therapy when a new computer tomography scan showed pancreatic cancer relapse and hence prompted 2nd line chemotherapy with gemcitabine. CONCLUSIONS: Polymyositis associated with pancreatic cancer may respond to glucocorticoids along with cancer specific treatment.

Neurotoxicity caused by the treatment with platinum analogues.

Platinum agents (cisplatin, carboplatin, and oxaliplatin) are a class of chemotherapy agents that have a broad spectrum of activity against several solid tumors. Toxicity to the peripheral nervous system is the major dose-limiting toxicity of at least some of the platinum drugs of clinical interest. Among the platinum compounds in clinical use, cisplatin is the most neurotoxic, inducing mainly sensory neuropathy of the upper and lower extremities. Carboplatin is generally considered to be less neurotoxic than cisplatin, but it is associated with a higher risk of neurological dysfunction if administered at high dose or in combination with agents considered to be neurotoxic. Oxaliplatin induces two types of peripheral neuropathy, acute and chronic. The incidence of oxaliplatin-induced neuropathy is related to various risk factors such as treatment schedule, cumulative dose, and time of infusion. To date, several neuroprotective agents including thiol compounds, vitamin E, various anticonvulsants, calcium-magnesium infusions, and other nonpharmacological strategies have been tested for their ability to prevent platinum-induced neurotoxicity with controversial results. Further studies on the prevention and treatment of neurotoxicity of platinum analogues are warranted.

Sustained complete remission of human epidermal growth factor receptor 2-positive metastatic breast cancer in the liver during long-term trastuzumab (Herceptin) maintenance therapy in a woman: a case report.

INTRODUCTION: This case report and short review discusses how long trastuzumab should be continued in metastatic breast cancer, the safety issues in case of pregnancy and the risk of relapse with trastuzumab cessation. CASE PRESENTATION: We present the case of a 34-year-old Caucasian woman with human epidermal growth factor receptor 2-positive metastatic breast cancer in the liver who achieved prolonged complete remission within six months of receiving trastuzumab (Herceptin) in combination with vinorelbine and gemcitabine. The patient remains in complete remission seven years later and continues to receive trastuzumab as maintenance therapy. CONCLUSION: Trastuzumab-based therapies have greatly improved the survival rates of patients with human epidermal growth factor receptor 2- positive metastatic breast cancer. Despite such improvements, the safety of trastuzumab administration during pregnancy is yet to be defined.

Topoisomerase I and IIalpha protein expression in primary colorectal cancer and recurrences following 5-fluorouracil-based adjuvant chemotherapy.

PURPOSE: Human DNA topoisomerases I and II (topo-I and -II) are essential for vital cellular processes such as DNA replication, transcription, translation, recombination, and repair. In the present study, we correlate topo-I and -II expression and outcome after chemotherapy in primary and relapsed colorectal cancer. PATIENTS AND METHODS: Patients with colorectal cancer that had recurred, following surgery and adjuvant chemotherapy and underwent a second operation were included in the present study. All had undergone surgical resection of the primary tumor and received post-operatively 5-FU-based (5FU + Leucovorin, Mayo Clinic regimen) adjuvant chemotherapy. Tumor tissue was collected at the initial operation from the primary tumor and at the time of recurrence (during the second operation following chemotherapy). All tissue samples were analyzed for levels of expression of both topo-I and topo-IIa using standard three-step immunohistochemistry on paraffin sections. RESULTS: Forty patients were included. Levels of expression of topo-I and topo-II were higher in malignant cells from tumor recurrences compared to primary tumors (P = 0.0001 for both). There was a statistically significant positive relationship between patients age and levels of topo-I (P = 0.011) and topo-II (P = 0.011) expression. CONCLUSIONS: The study results reported here underscore the role of topoisomerase expression in colorectal cancer and suggest a potential role in tumor recurrence.

Gabapentin monotherapy for the treatment of chemotherapy-induced neuropathic pain: a pilot study.

OBJECTIVE: This study was conducted to investigate the efficacy and safety of gabapentin monotherapy in the management of chemotherapy-induced neuropathic pain. PATIENTS: Seventy-five cancer patients who had previously received chemotherapy, and had experienced at least one symptom of neuropathic pain were included in the intervention group. They received a fixed low-dose of gabapentin (800 mg/day). The control group consisted of 35 cancer patients with similar treatment history and symptomatology, who refused treatment with gabapentin and, therefore, received a fixed-dose combination of naproxen and codeine/paracetamol. OUTCOME MEASURES: Patients were grouped in three categories according to the severity of their neuropathic symptoms at baseline: mild, moderate, and severe. Analgesic efficacy of the study drug was assessed by means of a patient-answered questionnaire. Four stages of analgesic response were established: complete, partial, minor, and no response. RESULTS: All patients completed the study and were evaluable. In the intervention arm, gabapentin led to a complete response in 25.3% of patients (19/75), partial response in 44% (33/75), minor response in 25.3% (19/75), and no response in 5.3% (4/75). The response to gabapentin correlated with the severity of the underlying neurotoxicity. Approximately 25% of patients receiving gabapentin experienced mild somnolence, but none discontinued it. In the control group, none experienced complete response (0/35), while partial, minor, and no response were observed in 5.7% (2/35), 45.7% (16/35), and 48.6% (17/35), respectively. Compared with the control group, gabapentin therapy led to a statistically significant better response in patients of each baseline neurotoxicity group. CONCLUSIONS: Gabapentin monotherapy seems to be well tolerated and useful for the management of chemotherapy-induced neuropathic pain.

Cardiotoxicity of fluoropyrimidines in different schedules of administration: a prospective study.

BACKGROUND: Cardiotoxicity associated with 5-Fluorouracil (5FU) administration has been infrequently reported in literature, albeit various series of acute coronary syndromes have recorded a low but definite incidence of the above toxicity. In the present study, patients undergoing 5FU-based and oral capecitabine (Xeloda-based chemotherapy were tested for the potential development of cardiac-related symptoms during their administration. PATIENTS AND METHODS: Six hundred and forty-four patients entered the study. Those experiencing any cardiac-related symptoms during 5FU infusion or oral capecitabine were subjected to ECG and serum cardiac enzymes determination. If cardiotoxicity was confirmed, 5FU infusion or oral capecitabine were interrupted, sublingual nitrates administered and cardiac monitoring initiated, while patients with >two-fold enzyme elevation were followed in a coronary care unit for at least 72 h. Cases with acute myocardial infarction were excluded from further 5FU or oral capecitabine treatment. RESULTS: Overall 26 patients (4.03%) developed symptoms and/or ECG abnormalities due to 5FU and capecitabine. Patients with continuous 5FU infusion presented a higher incidence of cardiotoxicity [14/209; 6.7%, 95% confidence interval (CI) = 3.3-10.1%] than the remaining (7/317; 2.3%, 95% CI = 0.8-3.3%) (P < 0.012). Specifically, an increased incidence of cardiac-related events was encountered in patients with continuous 24-h 5FU + LV infusion for 5 days (12.5%, 95% CI = 2.3-22.7%) rather than in patients with the same schedule without LV (5.3%, 95% CI = 1.95-8.67%) (P < 0.027), as well as in patients with short 5FU + LV administration (2.4%, 95% CI = 0.9-3.9%) (P < 0.019). Overall, 3/54 patients (5.5%, 95% CI = -0.6-11.1%) on oral capecitabine developed cardiac-related events. Seven out of the 20 patients suffered an acute myocardial infarction, 6 developed ischemia only, while 4 more patients had ECG consistent with coronary vasospasm and 3 with conduction disturbances, of which one subsequently died. Patients administered oral capecitabine had a similar incidence of cardiac-related events; 1/22 (4.5%) patients with advanced breast cancer and 2/32 (6.2%) with colorectal cancer. CONCLUSIONS: The present study supports the toxic effect of 5-FU on the myocardium, which is largely schedule-dependent, whereas a low but finite risk of such toxicity has been observed with oral capecitabine. A high level of alertness is required when using fluoropyrimidines (i.v. 5FU or oral capecitabine), while their toxic effect on the coronary endothelium and myocardium merits further investigation.

Aspects of the association between leishmaniasis and malignant disorders.

Given the prevalence of leishmaniasis and cancer, the co-existence of these two diseases may be merely coincidental. However, a number of epidemiological, experimental and laboratory studies suggest that an association between these two entities does exist. The aim of this review is to summarise the occurrence of leishmaniasis as an opportunistic infection associated with malignant disorders and to present the available literature potentially linking this infection with the development of cancerous lesions. We searched electronic databases and evaluated 37 studies involving 44 patients. Four different types of association between leishmaniasis and cancer were established: leishmaniasis mimicking a malignant disorder, such as lymphoma; leishmaniasis arising as a difficult to diagnose and treat infection among patients receiving chemotherapy for various malignant disorders; simultaneous diagnosis of leishmaniasis and a neoplastic disorder in the same tissue samples of immunocompromised patients; and direct involvement of Leishmania spp. in the pathogenesis/occurrence of malignant lesions, especially of the skin and mucous membranes. The main conclusion of this review is that leishmaniasis can directly or indirectly affect the presentation, diagnosis and course of various malignant disorders and it should be considered in the differential diagnosis of malignancies in geographic areas where it is endemic and/or in patients with travel history to these areas.

Sequential administration of 5-fluorouracil (5FU)/leucovorin (LV) followed by irinotecan (CPT-11) at relapse versus CPT-11 followed by 5-FU/LV in advanced colorectal carcinoma. A phase III randomized study.

PURPOSE: The purpose of the present study was to evaluate the differences in the sequence of administration of 5-fluorouracil (5-FU)/leucovorin (LV) followed by irinotecan (CPT-11), or CPT-11 followed by 5-FU/LV in advanced colorectal cancer (ACC). PATIENTS AND METHODS: Chemotherapy-naïve patients with ACC were allocated to the following treatment groups: group A, a bolus of 20 mg/m(2) LV and 425 mg/m(2) 5-FU for 5 days until progression/relapse, and upon progression treatment with weekly CPT-11 (100 mg/m(2)), and group B, CPT-11 followed at progression/relapse by 5-FU/LV at the same doses and schedules as in group A. RESULTS: 120 patients were randomized to receive one of the two treatment sequences and their pretreatment characteristics were equally balanced between treatment arms. No statistically significant difference was found in the objective response rate to CPT-11 (p = 0.45); partial response (PR) was 23.3% for group A patients and 33.3% for group B. Following documented progression and second line treatment there was a significant difference between the response rate in group A (23.3%) and group B where no patients were found to respond to second-line treatment with 5-FU/LV (p = 0.024). The median overall survival was 42.0 weeks (range, 36.6-47.4 weeks) for group A and 32.0 weeks (range, 28.2-35.8 weeks) for group B. The median time to progression for patients in group A following first-line 5-FU/LV was 18 weeks (range, 10-36 weeks) and 12 weeks (range, 10-16 weeks) for group B following first-line CPT-11 (p = 0.0005). Toxicity, according to WHO, was similar between groups. CONCLUSIONS: Treating patients with CPT-11 upon progression to 5-FU/LV treatment seems to be superior to the opposite sequence. We used these treatments as sequential monotherapies (at progression/relapse), and the best results are gained when 5-FU/LV is followed by CPT-11 at disease progression or relapse.

Docetaxel-ifosfamide combination in patients with HER2-non-overexpressing advanced breast cancer failing prior anthracyclines.

The feasibility of the docetaxel-ifosfamide combination, as well as the definition of maximum tolerated doses (MTD) in a previous phase I study, led us to continue evaluating the regimen in an extended phase II study in patients with HER2-non-overexpressing, anthracycline pre-treated advanced breast cancer. Patients with histologically confirmed metastatic breast cancer failing prior anthracycline-based chemotherapy were treated with docetaxel 100 mg/m2 over 1 h on day 1 followed by ifosfamide 5 g/m2 divided over days 1 and 2 (2.5 g/m2/day over 1 h), and recycled every 21 days with prophylactic granulocyte-colony stimulating factor (G-CSF) administration from day 3-until a neutrophil count >10,000/microl. Between March 1999 and June 2002, 71 patients with a median age of 55 years (range, 28-72) and performance status (World Health Organization; WHO) of 1 (range, 0-2) were treated; all were assessable for toxicity and 70 patients for response. Clinical response rates (RRs), on an intention-to-treat basis were: 41/71 [58%; 95% CI, 46.5-69.5%]; 7 complete remissions (CRs), 34 partial remissions (PRs), 15 stable disease (SD) and 15 progressive disease (PD). The median response duration was 7.5 months (2-28 months), median time-to-progression (TTP) 6 months (0.1-30 months), and median overall survival (OS) 12 months (0.1-36 months). Grade 3/4 toxicities included; neutropenia in 63% of patients-with 52% developing grade 4 neutropenia (>or=7 days) and in 11% of these febrile neutropenia (FN), while no grade 3/4 thrombocytopenia was observed. Other toxicities included; peripheral neuropathy grade 2 only in 7%, grade 1/2 reversible central nervous system (CNS) toxicity in 11%, no renal toxicity, grade 2 myalgias in 7%, grade 3 diarrhea in 4%, skin/nail toxicity in 11%, and grade 1/2 fluid retention in 28% of patients. The present report has demonstrated encouraging activity of the docetaxel-ifosfamide combination in anthracycline-pretreated, HER2-negative advanced breast cancer. Therefore, future randomized phase III studies versus single-agent docetaxel or currently established combinations of the latter with other agents in this setting with established clinical activity, such as capecitabine or gemcitabine, will be warranted.

A phase I-II study of bi-weekly gemcitabine and irinotecan as second-line chemotherapy in non-small cell lung cancer after prior taxane + platinum-based regimens.

PURPOSE: Treatment options in patients with recurrent non-small cell lung cancer (NSCLC) remain limited as a result of poor activity of most agents after failure of platinum-based therapy. In the present phase I-II study, we evaluated the feasibility and efficacy of bi-weekly gemcitabine (GEM) + irinotecan (CPT-11) in patients with relapsed NSCLC. PATIENTS AND METHODS: Patients with advanced NSCLC, WHO-performance status (PS)

A simplified premedication protocol for one-hour paclitaxel infusion in various combinations.

BACKGROUND: Many investigations have focused on optimal doses/schedules since regulatory agency approval of paclitaxel (Taxol). Paclitaxel is generally administered at doses of 175-225 mg/m2 over 3 hours or 135-175 mg/m2 over 24 hours, every 3 weeks. The purpose of this study was to simplify administration and render it suitable and practical in the outpatient setting. Using this rationale, the duration of administration was decreased to one hour, with a minimized premedication regimen. MATERIAL/METHODS: One hundred patients who were to receive paclitaxel-based chemotherapy combinations entered the study. Tumor types were non-small-cell lung cancer (NSCLC, n=40), small-cell lung cancer (SCLC, n=18), breast cancer (n=12), head and neck cancer (n=16), and ovarian cancer (n=14). Sixty patients received paclitaxel at 175 mg/m2 and the remaining 40 at 225 mg/m2. The premedication regimen consisted of a single dose of dexamethasone 20 mg, dimethindene maleate (Fenistil) 4 mg, and ranitidine (Zantac) 50 mg, followed by the standard antiemetic therapy. Paclitaxel was always administered before other chemotherapeutic agents, i.e. ifosfamide and/or platinum compounds, except for breast cancer, where epirubicin preceded paclitaxel administration. RESULTS: Hypersensitivity reactions were recorded in 7 patients (7.0%) and were not influenced by age, gender, disease, dose schedule, or cycles of therapy. No serious adverse events were observed. CONCLUSIONS: The simplified administration dose schedule for paclitaxel is safe and accommodates its combination with other cytostatic agents.

Analgesic activity of high-dose intravenous calcitonin in cancer patients with bone metastases.

We undertook a prospective, nonrandomized study with the objective to evaluate the efficacy of salmon calcitonin (sCT) in controlling pain secondary to bone metastases. Our study population consisted of 45 cancer patients with bone metastases (26 men) with a mean age of 64 years (range, 48-70) who had completed chemotherapy, hormonal therapy and radiation therapy at least 30 days prior to enrollment in the study, and had intractable pain despite the use of common analgesics (acetaminophen, nonsteroidal anti-inflammatory agents, opioids) and bisphosphonates. The study medication was a 300-IU dose of sCT administered intravenously daily for 5 consecutive days and repeated every two weeks until no response was noticeable. The analgesic efficacy of sCT was evaluated by means of Huskisson's visual analogue scale and Keele's pain scale; the daily consumption of analgesic drugs and performance status were also monitored. None of the patients managed to completely discontinue the use of other analgesics, but 5 patients (11% of the total number) had an analgesic response that lasted 4 weeks and less than 5% of the patients continued to respond for 6 weeks. No significant side effects were observed. Our data show that intravenous calcitonin administered in a relatively high dose has a very limited therapeutic potential as an adjuvant analgesic for a short period of time in selected cancer patients with bone metastases.

Spontaneous remission of acute myeloid leukemia associated with GnRH agonist treatment.

Spontaneous remission of acute myeloid leukemia (AML) in adults is a rare but well documented phenomenon. This study reports on a 64-year-old male patient with acute myelogenous leukemia (AML-M4, according to the French-American-British classification) that was developed on a background of chronic myelomonocytic leukemia (CMML) and then underwent remission after treatment with the gonadotropin-releasing hormone agonist (GnRH agonist) triptorelin for presumed prostate cancer. Remission persisted for at least 4 years before the patient was lost to follow-up. To the author' knowledge, this is the first report of remission in an AML-M4 case associated with hormone manipulation. Possible mechanisms of this phenomenon are discussed.

A phase II study of the docetaxel-ifosfamide-carboplatin combination in advanced non-small-cell lung cancer.

PURPOSE: In the present phase II study we evaluated the docetaxel-ifosfamide-carboplatin (DICb) combination in the outpatient setting in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with advanced NSCLC (stages IIIB/IV), WHO performance status (PS) <2, and no prior chemotherapy were eligible. Chemotherapy drug doses were: docetaxel: 80 mg/m2, ifosfamide: 3.5 g/m2, and carboplatin at a target area under the curve of 5 (based on Calvert's formula), all on day 1, followed by prophylactic G-CSF. RESULTS: Fourty patients were entered and all are evaluable for response and toxicity: median age: 64 (48-72); PS: 1 (0-1); gender: 29 males/11 females; stages: IIIB: 13 (33%), IV: 27 (67%). Metastatic sites at diagnosis included: lymph nodes: 25; bone: 7; liver: 4; brain: 5; lung nodules: 13; adrenals: 6. Responses were as follows: 22/40 [55%; 95% confidence interval (CI), 54-81%] evaluable patients responded: 4 complete responses, 18 partial responses, 11 had stable disease, and 7 had progressive disease. The median response duration was 7 months (range 2-14 months), median time to progression 9 months (range 2-18 months) and median overall survival 11 months (range 3-46+ months). 1-year survival was 47.5%. Grade 3/4 toxicities included: neutropenia 28/40, with 12 developing grade 4 and 12% febrile neutropenia, thrombocytopenia grade 3: 3/40 and grade 4: 1/40, no grade 3 neuropathy, grade 1 CNS toxicity in 3, no renal toxicity, 8 grade 2 diarrhea and 4 grade 3 vomiting. CONCLUSION: In the present phase II study the DICb combination yielded important activity and good tolerability in advanced NSCLC.

Cerebrospinal fluid tumor marker levels in predicting response to treatment and survival of carcinomatous meningitis in patients with advanced breast cancer.

BACKGROUND: The aim of this study was to evaluate the predictive value of cerebrospinal fluid (CSF) tumor marker levels in patients with breast cancer and carcinomatous meningitis. MATERIAL/METHODS: Serial CSF and serum tumor marker (CEA, CA-15.3, CA-125, and CA-19.9) measurements were performed in five patients with breast cancer developing carcinomatous meningitis in an attempt to correlate these with clinical outcome under treatment. RESULTS: CSF tumor marker levels correlated with response to treatment and outcome in each patient; despite achieving negative CSF cytology after therapy, in two patients it heralded disease progression. CONCLUSIONS: Given our findings, CSF tumor marker evaluation may provide a reliable means and surrogate end-points of monitoring response of carcinomatous meningitis to treatment. Therefore, large studies to assess the value of CSF tumor marker changes in carcinomatous meningitis are warranted.