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G Cartei

Publications and source records attributed to G Cartei.

At least 19 recordsLinked to original sources
PubMed2006

In vitro basis for schedule-dependent interaction between gemcitabine and topoisomerase-targeted drugs in the treatment of colorectal cancer.

BACKGROUND: While combination of gemcitabine with anti-topoisomerase poisons is routinely used in oncology, little is known on the biological interactions between these drugs. DESIGN: To understand the cellular basis for this association, we hypothesized an interaction of the two agents at the topoisomerase level. A real-time RT-PCR method was designed to quantify topoisomerase expression after treatment with gemcitabine (GEM) in two human colon adenocarcinoma cell lines. Efficacy of drugs as single agents and in combination was analyzed on the basis of their cytotoxic effects. RESULTS: We showed that a) gemcitabine induces expression of all major eukaryotic topoisomerases (I, II alpha and beta) at definite times after drug administration; b) cytotoxicity was more relevant when cells were treated with GEM and the topoisomerase poison within a short period of time. In particular synergistic effects were found when the anti-topoisomerase II agent was given 3 h after gemcitabine or when the anti-topoisomerase I drug was delivered 3 h before or after the antimetabolite. CONCLUSIONS: These findings help explaining the effectiveness of the combined therapy GEM/topoisomerase poisons and suggest a drug administration protocol for clinical treatment.

Adenocarcinoma↗
PubMed2006

Topoisomerase I, II alpha and II beta mRNA expression in peripheral blood mononuclear cells of patients with solid tumor: preliminary results.

BACKGROUND: The pyrimidine antimetabolite Gemcitabine (G) (2',2'-difluorodeoxycytidine) is used against several malignancies G exerts its antitumour effect mainly by incorporation of its triphosphate metabolite (dFdCTP) into DNA. Subsequently, DNA polymerase adds one additional deoxynucleotide and DNA synthesis is interrupted. The nuclear enzymes topoisomerase I and II (TPs) are critical for DNA function and cell survival; they control, maintain and modify DNA topology during both replication and translation of genetic materials. These enzymes induce cuts in one or both strands of DNA, allowing strands to pass through the nick and then rejoining the nicked strand of DNA. Anti-topoisomerase (TPs-inhibitors) drugs exist and are largely used in chemotherapy, however, most often blindly of the cancer TPs status. AIM: To understand the best association between G and TPs-inhibitors, we studied: (a) Topoisomerases I, II alpha and II beta mRNA expression in Peripheral Mononuclear Blood Cells (PBMCs) of patients with solid tumor, after 1, 2, 3, 4, 5, 6 h after treatment with Gemcitabine (G); b) in vivo expression of TPs genes after administration of Gemcitabine (a topoisomerases up-regulating drug) combined with the TPs inhibitors drugs (TID) Topotecan (T) and Etoposide (E), added to the culture beneath 1 h after TPD treatment. TPs mRNA expression was measured by quantitative real-time RT-PCR in PBMCs. RESULTS: The administration of 1-h infused G is followed by a fast rise of TPs expression (P > 0.0001 Student's t test, paired data, each patient control of himself); TPs inhibitors, sequentially given after G, highly reduced the TPs rising (P > 0.0001). CONCLUSIONS: G induces a TPs increase. A rationale might be available for combination chemotherapy (G plus TPs inhibitors). The study is ongoing to enroll further patients.

Adult↗
PubMed2006

Simplified gemcitabine and platin regimen in patients with advanced or metastatic non-small cell lung cancer (NSCLC) to be proposed as neoadjuvant therapy.

BACKGROUND: Chemotherapy of non-small-cell lung cancer (NSCLC) has been improved by the use of cis-platin (P) and the pyrimidine antimetabolite gemcitabine (G) (2',2'-difluorodeoxycytidine). GP regimens currently used in Italy for NSCLC were and are mainly based on G day 1, 8 and 15; P on day 2, every 28 days (4 Day-Hospital admissions per cycle). However, the third G dose is frequently omitted because of myelo-toxicity, with a consistent dose decrease of both G and P in comparison with the intended dose. The 24-h lag time from 1(st) G and P has not reasonable clinical pharmacology base. AIM OF THE STUDY: To have a simplified GP regimen based on two Day-Hospital admissions per cycle, with G on day 1 and 8, P after G on day 8; every 21 days, with the goal to use it in the neoadjuvant setting. MATERIAL AND METHODS: The study was designed as a controlled, prospective, multicentre investigation, based on G (1500 mg/m(2)) on day 1 and 8, and P (100 mg/m(2)) on day 8 immediately following G, administered on a 3-week cycle. Quality of life (EORTC) was valuated in 46 patients out of 95 valuable patients. Restaging procedures were repeated after the 3rd and the 6th cycle. RESULTS: Enrolled patients were 105 (stage IV: 63: IIIB: 29; IIIA: 13). GP cycles were 488 (1 to 6 per patient) 95 patients had at least 3 cycles and 59 of them had further 3 cycles. Myelotoxicity >or= g3 was mainly neutropenia, easily amenable with symptomatic and GCSF therapies (12.6% neutropenic fever); PNS toxicity occurred in 17.9% of patients. QoL was ameliorated (P < 0.05). Therapy was tolerable and gave a Response Rate (RR) of 52.3% after 3 cycles (Intention-to-treat analysis) and of 57.9% in 95 valuable patients who received at least 3 therapy cycles. CONCLUSION: Present results confirm a good efficacy and/or synergism of G to P, with G on day 1 and 8 and P on day 8. This two day-hospital admissions regimen is at least as good as more complex GP regimens, and may be proposed in the neoadjuvant setting.

Adult↗
PubMed2006

Gemcitabine and liposomal doxorubicin in biliary and hepatic carcinoma (HCC) chemotherapy: preliminary results and review of the literature.

BACKGROUND: Advanced biliary tract cancers have a poor prognosis. Gemcitabine (G) as a single agent or in combination represents an active treatment option. Systemic chemotherapy in hepatocellular carcinoma represents a palliative treatment. Gemcitabine in combination with Liposomal Doxorubicin (LD) may represent an active treatment option. PATIENTS AND METHODS: Clinical trials for biliary and hepatic carcinoma have been reviewed. RESULTS: We obtained RC (1 pt), RP (4 pts), SD (8 pts) and seven pts had PD (RR 25% and SD 40%). Our chemotherapy regimen was Gemcitabine 1000 mg/m(2) d 1 and 8, Liposomal Doxorubicin 30 mg d 1, q 28. Patients were 21 (17 M), aged 44 to 78 (median 63 yrs). Only in 8 pts we observed G 3-4 haematological toxicity, thrombocytopenia and neutropenia (7 G3, 1 G4).

Adenocarcinoma↗
PubMed2003

Prognostic significance of the detection of tumour cells in peripheral blood stem cell collections in stage II and III breast cancer patients treated with high-dose therapy.

The purpose of this study was to evaluate the incidence and extent of tumour cell contamination in bone marrow specimens and stem cell collections from 34 breast cancer patients undergoing high-dose therapy as adjuvant treatment, and to determine the prognostic significance for the clinical outcome. Tumour cell contamination was evaluated by flow cytometry using a double-colour test and an anti- Pan cytokeratin (CK) antibody. Two out of 34 (6%) baseline bone marrow specimens, none of seven marrow harvests and nine out of 32 aphereses (28%) mobilised from seven out of 27 patients (26%) contained CK+ cells. Tumour contamination was more frequent in patients with 10 or more involved lymph nodes and in those who received a shorter course of adjuvant chemotherapy before mobilisation. At a median follow-up of 43 months, 24 patients are in complete remission, whereas 10 patients experienced recurrence. Out of the 10 patients who relapsed, five (50%) had CK+ peripheral blood stem cell (PBSC) collections, whereas disease recurrence was seen in only two out of 24 (8%) patients who received CK- products (P=0.02). Moreover, CK+ PBSC collections were associated with a significantly shorter event-free survival and overall survival. CK+ collection is an unfavourable prognostic factor for patients treated with high-dose therapy. Whether the negative impact on clinical outcome depends on reinfusion of tumour cells or whether it simply indicates a larger disease extension is still unclear.

Adult↗
PubMed2003

Preoperative chemoradiotherapy in cancer of the thoracic esophagus.

Surgery with or without adjuvant radiotherapy (RT) is the standard treatment of esophageal cancer. Preoperative radio- and chemotherapy (CT) have been introduced to improve prognosis. We report a phase II prospective non-randomized trial of preoperative RT (42 Gy/25) plus CT (cisplatin 20 mg/mq/day plus 5-fluorouracil 600 mg/mq/day, 1-5 weeks) for the treatment of thoracic esophageal cancer. From 1993, 50 patients were enrolled (40 men and 10 women, mean age 57 years, range 30-75 years). Squamous cell carcinoma accounted for 90% of cases; 10% were adenocarcinoma. Downstaging of the disease was obtained in 77.3% of cases; there were 13 (29.5%) complete responses (CR) and 21 (47.7%) partial responses (PR). Median survival was 28 and 25 months, respectively, for CR and partial response (PR) plus stable disease (SD) and progressive disease (PD) (P = 0.05). Progressive-free median survival was 22 and 17 months, respectively, for CR and PR + SD + PD (P = 0.08). Multimodal treatment of esophageal cancer showed promising results, although not significant, in terms of survival and disease progression for patients achieving a complete pathologic response.

Adenocarcinoma↗
PubMed2003

Dose finding of ifosfamide administered with a chronic two-week continuous infusion.

PURPOSE: Ifosfamide (IFO) is an active drug in several malignancies. A short-term 3- to 7-day (A) continuous infusion (c.i.) has been used in different tumor types. The 14-day c.i. (B) has been investigated in advanced breast cancer and in soft tissue sarcoma patients at a fixed daily dose. The tolerance and response rate (RR) of therapies A and B has been considered encouraging. AIM: To study the 14-day c.i. IFO schedule, every 28 days, with a dose-finding approach. METHODS: From January 1998 to December 2001, 34 pretreated patients with advanced malignancy and disease progression were treated with c.i. IFO (and the same dose of mesna) from 400 to 1,000 mg/m(2)/24 h for 2 consecutive weeks every 28 days. An elastomeric pumping device via an Infuse-a-Port((R)) or a Groshong((R)) catheter was used. RESULTS: A total of 159 cycles were evaluable for toxicity and results. No toxic deaths occurred. Three patients (8.8%) had a severe acute allergic cutaneous reaction with various grade 3-4 toxicities requiring hospitalization and therapy was stopped at day 6 of the first cycle, 7 and 12 of the second cycle respectively. In the other 31 patients, grade 4 neutropenia occurred in 6 (19.3%) and it represented the main toxicity. There was a positive relationship between the IFO dose step and neutropenia (p = 0.001). A positive relationship was observed between the RR and the received total IFO dose (g) (p < 0.004). Twelve patients out of 31 had progressive disease (PD) (38.7%), 8 had partial remission (PR) (25.8%), and 11 maintained a steady state (35.5%). Six of the 12 patients (50%) with PD and 2 of the 8 PRs (25%) had bone metastases. CONCLUSIONS: IFO c.i. is generally well tolerated, but acute untoward allergic reactions can occur. In chemotherapy-pretreated patients the recommended daily dose of continuously infused IFO for 14 days every 4 weeks is 900 mg/m(2)/day, together with mesna at the same dose schedule.

Adolescent↗
PubMed2001

A phase II study of induction chemotherapy with gemcitabine (G) and cisplatin (P) in locally advanced non-small cell lung cancer: interim analysis.

BACKGROUND: Gemcitabine-cisplatin (GP) combination is one of the most active and well tolerated regimens in advanced non-small cell lung cancer (NSCLC). The aim of this study is to evaluate the activity and toxicity of the GP regimen as a 21-day schedule in patients (pts) with stage IIIAN2-IIIB NSCLC. PATIENTS AND METHODS: From October 1997 to July 2000, 47 pts entered the study: 43 were eligible (40 men and three women); median age was 61 years (range 45-73); ECOG PS 0-1; histology was squamous (20 pts), adenocarcinoma (12 pts), large cell (five pts), and undifferentiated (six pts); stage was IIIAN2 (14 pts, 32.56%), and IIIB (29 pts, 67.44%). Malignant pleural effusion or superior vena cava syndrome was criteria of exclusion. Induction treatment consisted of three cycles of GP (G 1250 mg/m(2) i.v. on days 1 and 8, and P 100 mg/m(2) on day 8 every 3 weeks). Responding and stable pts underwent surgery (S) and/or radiotherapy (RT). RESULTS: Following a minimum of two cycles, 39 pts were evaluable for response and 42 for toxicity. Two pts had complete responses (CR; 5.2%), 24 had partial response (PR; 61.5%), eight had stable disease (SD; 20.5%), and five had progressive disease (PRO; 12.8%). WHO grades 3 and 4 anaemia, neutropenia and thrombocytopenia were observed in two, four and two pts, respectively; non-haematological toxicity was moderate. After induction, stable and responding pts received either RT (18 pts) or S+RT (13 pts). Among the 16 resected pts, a radical complete resection was possible in 13 cases (81.3%), whereas tumour down-staging was observed in nine pts (56.2%). CONCLUSION: GP, as a 3-week neoadjuvant schedule, appears a safe and active regimen.

Aged↗
PubMed2001

Surgical management of isolated bilateral adrenal metastases from colon carcinoma causing adrenal insufficiency.

Adrenal insufficiency due to histologically proven bilateral metastatic adrenal involvement from colon cancer has been clinically reported only twice. Surgical treatment of bilateral adrenal metastases is seldom performed, since other metastatic localizations are usually concomitant. To the best of our knowledge, we report the first case of relatively long-term disease-free survival after bilateral adrenalectomy in a patient with adrenal insufficiency due to bilateral metastases from colon carcinoma.

Adenocarcinoma↗
PubMed2000

Pharmacokinetics of intraperitoneal hyperthermic perfusion with mitoxantrone in ovarian cancer.

PURPOSE: Theoretical data and experimental assumptions indicate that intraperitoneal hyperthermic chemotherapy may play a role in the treatment of peritoneal carcinomatosis. The feasibility, tolerability and pharmacokinetics of intraperitoneal hyperthermic perfusion with mitoxantrone were studied in patients with pretreated ovarian cancer. METHODS: After cytoreductive surgery, 11 patients underwent intraperitoneal hyperthermic perfusion with mitoxantrone. A heated (42-43 degrees C) solution of the drug (28 mg/m2) was recycled through a perfusion apparatus into the abdominal cavity for 90 min. Treatment was repeated every month for two to four cycles. In six patients blood and peritoneal perfusate samples were collected at 0.5, 1, 1.5, 2, 4, 8, 16 and 24 h after drug administration and mitoxantrone was assayed by an HPLC method. RESULTS: Although treatment was generally well tolerated, all patients developed transient intestinal subocclusion. Maximal mitoxantrone plasma concentrations (Cmax), times to Cmax (Tpeak) and area under the curves (AUC) were highly variable between subjects (Cmax 14-337 ng/ml; Tpeak 0.5-8 h; AUC 222-4130 ng x ml(-1) x h). The plasma to peritoneal fluid AUC ratio was significantly higher during the second (0.177) than during the first cycle (0.066), suggesting a cycle-dependent increase in systemic bioavailability. Furthermore, when comparing present data with those reported previously, hyperthermic perfusion may have lowered the mitoxantrone levels in the peritoneal fluid without greatly influencing plasma levels. CONCLUSIONS: Intraperitoneal mitoxantrone administered under hyperthermia to advanced ovarian cancer patients is feasible and well tolerated. Mitoxantrone pharmacokinetics may be altered by repeated intraperitoneal administration (increased bioavailability) and by hyperthermic perfusion (possibly, increased peritoneal tissue uptake).

Adult↗
PubMed2000

Physicians' attitudes to and problems with truth-telling to cancer patients.

Disclosure of a diagnosis of cancer to patients is a major problem among physicians in Italy. The aim of the study was to assess physicians' attitudes to and opinions about disclosure. A convenience sample of 675 physicians in Udine (North Italy) completed a ten-item questionnaire. About 45% indicated that, in principle, patients should always be informed of the diagnosis, but only 25% reported that they always disclosed the diagnosis in practice. Physicians with a surgical specialization employed in general hospitals endorsed disclosure of the diagnosis more frequently than GPs and older physicians. One third of the responding physicians persist in the belief that the patients never want to know the truth. Hospital doctors considered the hospital, rather than the patient's home, was the most appropriate place to inform the patients. The opposite result was found among GPs. Almost all the physicians endorsed the involvement of family members when disclosing the diagnosis, but, at the same time they also indicated that families usually prefer their ill relative not to be informed. Ninety-five per cent of physicians believed that the GP should always be involved in the processes of diagnosis and communication, and 48% indicated that the GP should communicate the diagnosis to the patient (as opposed to the physician who made the diagnosis). Having guidelines for breaking bad news to patients was indicated as an important need by 86% of the responding physicians. Despite changes in medical education, improvement of communication skills in dealing with cancer patients and their families represents an important need in healthcare settings.

Adult↗
PubMed2000

Oral 5-fluorouracil in squamous cell carcinoma of the skin in the aged.

Multiple or recurrent squamous cell skin carcinoma is a rare tumor in the aged. These patients are currently treated with 5-fluorouracil (5-FU) cream as a local chemotherapy; in cases in which the disease progresses, few treatments are available. Two reports deal with the treatment of progressive squamous cell skin carcinoma with systemic 5-FU, but in only eight patients age less than 70 years. We prospectively investigated oral 5-FU therapy in 14 consecutive patients (average age 76 1/2 years) with histologically proven squamous cell skin carcinoma. The disease was aggressive, multiple, or recurrent and had not been eradicated by surgery, radiation therapy, topical 5-FU cream, and non-5-FU chemotherapy. Oral 5-FU was administered as mannitol-coated 5-FU tablets at the daily dose of 175 mg/m2 for 3 weeks every 5 weeks. Toxicity, effectiveness, quality of life, and compliance to therapy were evaluated. Total cycles amounted to 55 (range: 2-6, mean: 4 for each patient) at an average dose intensity of 740 mg/m2/week for from 12 to 36 weeks. Only gastrointestinal toxicity World Health grade I occurred. Quality of life and compliance to therapy were 90%. Therapy induced measurable improvement in nine patients (64.3%): two partial remissions (14.3%), three minimal remissions (21.4%), and four arrests of disease (28.6%) with a median duration of 30+ months. The study ended because of a lack of patients. We can conclude that, if elderly patients require chemotherapy because of progressive multiple or advanced squamous cell skin carcinoma, appreciable results may be obtained with oral 5-FU as a single agent.

Administration, Oral↗
PubMed1999

Squamous cell carcinoma arising at the base of the penis in a burn scar(1).

Squamous cell carcinoma developed after 32 years in a burn scar located on the ventral surface of the penis at the penoscrotal junction. The origin of squamous cell carcinoma in burn scars is a rare and not completely understood phenomenon. To the best of our knowledge, this is the first documented case of such an event in the penis because of the extreme rarity of genital burns.

Burns↗
PubMed1999

Cisplatin and gemcitabine in non-small-cell lung cancer.

The nucleoside analogue, gemcitabine, has shown activity as a single agent in the treatment of metastatic non-small-cell lung cancer (NSCLC), producing consistent response rates of 20% and above. Because of its unique mechanism of action and its non-overlapping toxicity with other active agents, gemcitabine is an attractive candidate for trials in combination with other cytotoxic agents. In preclinical models, the cisplatin-gemcitabine combination suggested synergy between the two drugs. In phase I-II studies, response rates are as high as 54% when gemcitabine is combined with cisplatin, both in stage III and IV NSCLC. The gemcitabine-containing regimens showed a favourable safety-efficacy profile and compared well with standard regimens used in NSCLC. These preliminary results must be validated by large randomised trials comparing gemcitabine-containing regimens with NSCLC reference chemotherapy regimens.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Vinorelbine, bleomycin and methotrexate as a salvage therapy for patients with head and neck squamous carcinoma in relapse after cisplatin/fluorouracil.

BACKGROUND: Cisplatin (CDDP) and 5-fluorouracil (5-FU) represent the standard chemotherapy for advanced/recurrent head and neck squamous carcinoma (HNSC); however, the duration of response is often short, with a median survival of only five to six months. PATIENTS AND METHODS: Patients with HNSC were treated with vinorelbine 20 mg/m2 and methotrexate 50 mg/m2 every week and bleomycin 15 mg/m2 every two weeks. All patients were previously treated with a CDDP/5-FU regimen. RESULTS: Forty-eight patients were evaluable for response and toxicity. After a median follow-up of 15 months, 16 patients are still alive and 32 have died. We had one complete response (2%), 12 partial responses (25%) (overall response rate 27%; 95% CI: 14%-39%), 11 stabilizations (23%) and 24 progressions (50%) of disease. Neutropenia grade 3-4 was seen in 12 patients; peripheral neurotoxicity in two patients. There were no toxic deaths. CONCLUSIONS: This regimen, administered in an outpatient setting, revealed some activity as a second-line treatment in patients with HNSC, with acceptable toxicity.

Aged↗