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Biomedical subjects

L Crino

Publications and source records attributed to L Crino.

15 recordsLinked to original sources
PubMed2006

Insulin-like growth factor receptor 1 (IGFR-1) is significantly associated with longer survival in non-small-cell lung cancer patients treated with gefitinib.

BACKGROUND: The aim of the study was to assess whether loss of PTEN and expression of insulin-like growth factor receptor 1 (IGFR-1) could be responsible for intrinsic resistance to the tyrosine kinase inhibitor (TKI) gefitinib. PATIENTS AND METHODS: One hundred and twenty-four gefitinib-treated patients with advanced non-small-cell lung cancer (NSCLC) were analyzed for PTEN and IGFR-1 expression by immunohistochemistry. RESULTS: IGFR-1 was evaluated in 77 patients and resulted positive in 30 (39.0%). IGFR-1 expression was not significantly associated with clinical or biological characteristics. No difference in response to gefitinib treatment (16.7% versus 12.8%, P = 0.74) and time to progression (2.6 versus 3.06 months, P = 0.83) was observed between IGFR-1+ and IGFR-1-. Median survival was significantly longer in IGFR-1+ patients (17.8 versus 7.3 months, P = 0.013). PTEN expression was successfully evaluated in 93 cases. Loss of PTEN was detected in 19 tumors (20.4%) and was not associated with any clinical or biological characteristic. No difference in terms of response, time to progression and survival was observed between PTEN+ and PTEN- patients. In multivariable analysis IGFR-1 negative status was significantly associated with higher risk of death (hazard ratio 2.21, P = 0.012). CONCLUSIONS: IGFR-1 expression and loss of PTEN are not associated with intrinsic resistance to gefitinib. Clinical relevance of these two biomarkers as determinant for acquired resistance, and the prognostic role of IGFR-1 expression in patients not exposed to TKIs should be evaluated further.

Adult↗
PubMed2005

HER3 genomic gain and sensitivity to gefitinib in advanced non-small-cell lung cancer patients.

In non-small-cell lung cancer (NSCLC), sensitivity to tyrosine kinase inhibitors (TKIs) is associated with activating mutations and genomic gain of the epidermal growth factor receptor (EGFR). Preclinical data suggested that HER3 overexpression increases sensitivity to TKIs. A total of 82 NSCLC patients treated with gefitinib (250 mg), and previously evaluated for EGFR and HER2 status by fluorescence in situ hybridisation (FISH) and DNA sequencing, and for Phospho-Akt status by immunohistochemistry, were investigated for HER3 genomic gain by FISH. Patients with high polysomy and gene amplification were considered as HER3 FISH positive (+). HER3 FISH+ pattern was significantly associated with female gender (P=0.02) and never smoking history (P=0.02). Patients with HER3+ tumours (26.8%) had a significantly longer time to progression (3.7 vs 2.7, P=0.04) than patients with HER3- tumours, but not a significantly better response rate or survival. Patients with EGFR+/HER3+ tumours had higher objective response rate (36.4 vs 9.9%, P=0.03) and time to progression (7.7 vs 2.7 months, P=0.03) than patients with EGFR- and/or HER3- tumours, but no significantly longer survival. No difference in response was observed according to HER3 status in patients with EGFR+ tumours. Patients with HER2+/HER3+ tumours had similar outcome as patients with HER2- and/or HER3- tumours. Significantly different clinical end points were not observed between patients with HER3+/P-Akt+ and HER3- and/or P-Akt- tumours. Genomic gain for HER3 is not a marker for response or resistance to TKI therapy in advanced NSCLC patients.

Antineoplastic Agents↗
PubMed2005

Primary chemotherapy with gemcitabine, epirubicin and taxol (GET) in operable breast cancer: a phase II study.

This trial was conducted to assess the activity and tolerability of the gemcitabine, epirubicin, taxol triplet combination in patients with operable breast cancer. After core biopsy, 43 women with stage II-IIIA breast cancer were treated with gemcitabine 1000 mg m(-2) over 30 min on days 1 and 4, epirubicin 90 mg m(-2) as an intravenous bolus on day 1, and taxol 175 mg m(-2) as a 3-h infusion on day 1, every 21 days for four cycles. The primary end point was the percentage of pathological complete responses (pCR) in the breast; secondary end points were tolerability, clinical response rates, overall and progression-free survival, tumour biomarkers before and after primary chemotherapy (PCT). All patients were included in safety and survival analyses; 41 eligible patients were evaluated for response. The overall clinical response rate was 87.8% (95% CI 77.8-97.8), with 26.8% complete responses (95% CI 13.3-40.3). A pCR in the breast was observed in six patients (14.6%; 95% CI 3.8-25.4); 15 patients (36.6%; 95% CI 21.9-51.3) had negative axillary lymph nodes. Grade 4 neutropenia was observed in 67.4% of the patients; febrile neutropenia occurred in 1.9% of cycles (granulocyte colony-stimulating factor was used in 3.2% of the cycles to shorten the duration of neutropenia). A statistically significant difference between Mib-1 at baseline (> or =20% in 71.4% of the patients) and at definitive surgery (28.6%, P < 0.05) was observed. The gemcitabine, epirubicin, taxol regimen is active and well tolerated as PCT for operable breast cancer. This combination allows the administration of full doses of active agents with a low incidence of febrile neutropenia.

Adult↗
PubMed2005

Efficacy of gemcitabine plus platinum chemotherapy compared with other platinum containing regimens in advanced non-small-cell lung cancer: a meta-analysis of survival outcomes.

PURPOSE: Gemcitabine-platinum combination activity has been clearly established in a number of phase II studies. It has also been compared against other combinations in many phase III trials. It is generally believed that all such regimens have an equivalent impact on survival. This meta-analysis aims to quantify the treatment effect of gemcitabine plus a platinum agent in the treatment of advanced NSCLC and compare the combination to other regimens used globally. DESIGN: Data from a total of 4556 patients from 13 randomized trials investigating gemcitabine in combination with a platinum agent versus any other platinum-containing regimen were included in a meta-analysis of time-to-event outcomes. RESULTS: A significant reduction in overall mortality in favor of gemcitabine-platinum regimens was observed, hazard ratio (HR) 0.90 (95% CI: 0.84-0.96) with an absolute benefit at 1 year of 3.9%. Median survival was 9.0 months for the gemcitabine-platinum regimens and 8.2 months for the comparator regimens. Sub-group analysis of the first- and second-generation platinum-based comparator regimens also indicated a significant benefit for gemcitabine-platinum regimens, HR 0.84 (CI: 0.71-0.9985). Analysis of third-generation agent plus platinum regimens showed a non-significant trend favoring gemcitabine-platinum regimens, HR 0.93 (CI: 0.86-1.01). There was a significant decrease in the risk of disease progression in favor of gemcitabine-platinum regimens, HR 0.88 (CI: 0.82-0.93). An absolute benefit of 4.2% at 1 year was estimated. Median progression-free survival was 5.1 months for gemcitabine-platinum regimens compared with 4.4 months for the comparator regimens. Sub-group analysis indicated a statistically significant progression-free survival benefit for patients assigned to gemcitabine-platinum treatment compared to first- and second-generation platinum regimens, HR 0.85 (CI: 0.77-0.94), and third-generation agent plus platinum regimens, HR 0.89 (CI: 0.82-0.96).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

The gemcitabine/epirubicin/paclitaxel trials in advanced breast cancer.

Numerous trials have shown that the pharmacokinetic interferences of epirubicin (Ellence)/paclitaxel (Taxol) combinations produce less pharmacodynamic effect than doxorubicin/paclitaxel regimens. Paclitaxel is more easily combined when infused over 3 (as compared to 24) hours; the administration of optimal doses of both agents is important. Based on these findings, a phase II study was performed to evaluate the feasibility and activity of the combination of gemcitabine (Gemzar), epirubicin, and paclitaxel as first-line therapy in advanced breast cancer. Patients received gemcitabine at 1,000 mg/m2 on days 1 and 4, plus epirubicin at 90 mg/m2 on day 1, plus paclitaxel at 175 mg/m2/d on day 1 every 21 days. After six courses, patients less than 60 years old and in complete or partial remission or stable disease were treated with high-dose chemotherapy as consolidation treatment. The overall response rate was 92%, with 31% complete responses; 25 patients received high-dose chemotherapy, achieving a final overall response rate of 97%, with 47% complete responses. At a median follow-up of 25 months, median progression-free survival is 21 months. Grade 4 neutropenia was observed in 64% of patients. Other hematologic toxicities were mild. Mild to moderate peripheral neuropathy was experienced by 39% of patients; grade 2 or 3 mucositis occurred in 25% and 17% of patients, respectively. Based on these results, a multicenter trial has been started in seven Italian centers to confirm the feasibility of this regimen.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

[Role of gemcitabine in the treatment of advanced non-small cell lung cancer: review of the main phase II and phase III trials].

Marked advances in the treatment of non-small cell lung cancer (NSCLC) have been made thanks to new agents. Among these agents, gemcitabine appears to be a major compound in advanced stage NSCLC chemotherapy. To start with, several phase III trials (conducted in Europe and in the USA) studied the gemcitabine/cisplatin combination (GC): US study protocois compared GC to cisplatin alone, to the standard treatment (etoposide/cisplatin) or to platinum/taxane doublets; in these studies, as a result of treatment with GC, a higher survival rate was observed. A study conducted in Italy, which is undergoing analysis, observes GC versus paclitaxel/carboplatin versus cisplatin/vinorelbine. In addition, in newer clinical protocols, it was observed that gemcitabine combined with taxanes or with vinorelbine demonstrated efficacy at least equal to that of combinations with platinum analogs. Newer agents acting on epithelial growth factor are also undergoing evaluation.

Antimetabolites, Antineoplastic↗
PubMed2000

The influence of gemcitabine and cisplatin schedule on response and survival in advanced non-small cell lung cancer.

PURPOSE: Gemcitabine-cisplatin combinations are among the most active for the treatment of non-small cell lung cancer. Previous reports have suggested that the day of cisplatin administration affects both toxicity and drug delivery. We undertook this retrospective analysis to determine whether it also affects response and survival. PATIENTS AND METHODS: This was a retrospective analysis of six studies of gemcitabine and cisplatin. Gemcitabine, 1000-1500 mg/m(2) was administered on days 1, 8, and 15 of a 28 day cycle. In four studies cisplatin 100 mg/m(2) was administered with mannitol diuresis every four weeks on either day 1, day 2 or day 15. In two studies cisplatin 25-30 mg/m(2) was administered on day 1, 8 and 15. Standard prognostic factors including age, gender, stage, performance status, and histologic subtype were analyzed along with day of cisplatin administration. Single variable Cox proportional hazards regressions were performed. This was followed by multiple variable Cox proportional hazards regression, beginning with a full model containing terms for gender, age, performance status and stage. The least statistically significant terms were subsequently dropped from the model to reach a final model with only statistically significant variables. A similar approach was followed to fit a multiple variable logistic regression model to overall response data. RESULTS: Overall response rates were highest (36-46%) in the three studies that administered cisplatin on days 2 or 15, and these studies had the highest 1-year survival rates (52-58%). Survival was better for patients who received cisplatin on day 2 or 15 compared to those treated on either day 1 or weekly on days 1, 8, 15 (P=0.020). In the final model of the Cox regression analysis, survival was better for cisplatin on days 2 or 15 (hazard ratio=0.69, P=0.008) and female gender (hazard ratio=0.72, P=0.036). Only cisplatin delivery on day 2 or day 15 predicted for significantly better response (42 vs. 29%, P=0.036). CONCLUSION: In a 28 day cycle in which gemcitabine is administered day 1, 8 and 15, the best therapeutic index is achieved with cisplatin administration on day 2 or 15.

Adult↗
PubMed1993

A prospective analysis of chemotherapy following surgical resection of clinical stage I-II small-cell lung cancer.

Thirty-seven (37) consecutive patients with clinical Stage I (T1-2NO, Mo), and Stage II (T1-2N1 Mo) central small-cell lung cancer (SCLC) underwent complete surgical resection of the primary tumor. Ten patients were subsequently pathologically Stage I, 14 patients were Stage II, and 8 were Stage III (T3;N2). The pathologically Stage I, II, and III patients were then treated with chemotherapy consisting of cyclophosphamide (1 g/m2), doxorubicin (50 mg/m2), and vincristine 2 mg (CAV) every 3 weeks for six courses followed by prophylactic cranial irradiation (2000 cGy in 10 fractions). Median survival in Stage I patients is 162 weeks and calculated 5-year survival is 50%; for Stage II patients, median survival is 86 weeks and calculated 5-year survival is 35%. T3;N2 patients have a median survival of 63 weeks; calculated 5-year survival is 21%. Our data suggest surgery plus adjuvant chemotherapy and cranial irradiation results in long-term survival in early central SCLC. These data support the need for randomized surgical trials in Stage I, II, and III central SCLC.

Adult↗
PubMed1990

A randomized trial fo three cisplatin-containing regimens in advanced non-small-cell lung cancer (NSCLC): a study of the Umbrian Lung Cancer Group.

Survival in patients with locally advanced (stage III Mo) and metastatic (Ml) non-small-cell lung cancer (NSCLC) is short. Phase II studies have reported objective responses ranging from 20% to 60% using cisplatin-based chemotherapeutic regimens, yet few have shown improvement in median survival. In our phase II pilot studies with cisplatin (CDDP) and etoposide (VP-16), we observed a 26% response rate; with CDDP, VP-16, and mitomycin-C, a 38% response rate was obtained in advanced NSCLC patients. A total of 156 consecutive patients with locally advanced and metastatic NSCLC were randomized to one of three treatment arms to determine whether the chemotherapy protocols had any effect on response rate and median survival in a large, randomized study. Arm 1 consisted of CDDP (120 mg/m2 x 3 weeks); arm 2, of CDDP (120 mg/m2) and VP-16 (100 mg/m2 given i.v. on days 1-3), repeated every 3 weeks; and arm 3, of CDDP (120 mg/m2) and VP-16 (100 mg/m2 on days 1-3) given every 3 weeks, plus mitomycin C (10 mg/m2 on days 1, 21, and 42, then every 6 weeks, for a maximal dose of 100 mg). After 71 patients had been enrolled in the study, we stopped accrual in the CDDP arm due to a lack of response [1 complete response (CR) in 24 patients; 4%] and continued enrollment in the two combination-chemotherapy arms. In the CDDP/VP-16 arm a 30% response rate [1 CR, 18 partial responses (PRs)] was obtained, and in the CDDP/VP-16 mitomycin C arm a 26% response rate (4 CRs, 11 PRs) was seen among a total of 150 evaluable patients. Responses were observed in 31% of patients with favorable performance status (PS) (ECOG 0-1) vs 14% in patients with a poor PS (ECOG 2-3). Of patients with locally advanced disease (III Mo), 17 (33%) obtained an objective response, compared with 20 patients (20%) with metastatic disease. Median survival was 18 weeks in the CDDP arm, 35 weeks in the CDDP/VP-16 arm, and 37 weeks in the CDDP/VP-16/mitomycin C arm. The median survival in the multimodal chemotherapy arms was significantly greater than that obtained with CDDP alone. Toxicity was predominantly myelosuppression in the mitomycin C-containing arm (27%, wtto grade 3-4). Our study shows that combination chemotherapy using CDDP/VP-16 is active and safe in the treatment of advanced NSCLC patients with a good performance status. The addition of mitomycin C did not improve the therapeutic response.

Adult↗
PubMed1986

Vindesine and mitomycin C in chemotherapy: refractory advanced breast cancer.

Thirty-five unselected postmenopausal women with metastatic breast carcinoma, refractory to hormonal manipulation and/or chemotherapy, were treated with vindesine (3 mg/m2 day 1, then weekly for 6 weeks, then every other week) and mitomycin (12 mg/m2 day 1, then every 6 weeks). Thirty-one patients were evaluable for response. Two patients obtained a complete response (CR), three patients a partial response. Duration of the response in the two patients with CR was 24 and 16 months, respectively. Toxicity was mild, consisting of leukopenia and neurologic toxicity. Thrombocytopenia was not a significant clinical problem. Vindesine with mitomycin C, as administered in this study, is a safe, but marginally effective regimen for previously treated patients with metastatic breast cancer.

Adult↗
PubMed1977

Radioresistant inhibition of lymphoma growth in congenitally athymic (nude) mice.

Several murine tumors were used to determine whether the phenomenon of tumor inhibition in athymic "nude" mice reported previously could be extended to other tumor systems in nude as well as conventional mice. The results with the L5MF-22 tumor line were confirmed, and similar data were obtained with the K36 leukemia of AKR mice and the LAF-17 leukemia of B10.A origin. This phenomenon of tumor inhibition has been called, tentatively, radioresistant inhibition of tumor and may be explained by one of several possibilities. The immunological origin of such tumor inhibition is supported by various observations. The data on tumor cell proliferation in spleens and liver of lethally irradiated mice were similar to previous findings on hemopoietic histocompatibility-incompatible lymphomas. Additionally, the nude mice were stronger responders against lymphoma cells than were conventional hosts. Another explanation is that the tumor inhibition is due to natural cytotoxicity.

Animals↗
PubMedDate not supplied

Medical treatment of brain metastases from solid tumours.

Brain metastases (BrM) are estimated to occur in 20% to 40% of cancer patients, and two-thirds of them become symptomatic during their lifetime. Although every solid tumour may spread to the brain, the risk of developing BrM is higher in lung cancer, breast cancer and melanoma patients. Several findings suggest that the incidence of BrM is rising as a result of advances in imaging procedures and improvements in therapy, which leaves more cancer patients at risk as survival increases. The prognosis of patients with BrM is dependent on the type of the primary tumour. Breast cancer patients have better prognosis than those with BrM from lung, melanoma or colorectal cancer. Patients with BrM from renal cell carcinoma tend to have a poor prognosis. The optimal treatment of patients with BrM continues to evolve. Several factors interfere with the therapeutic strategy, such as histology of primary tumour, patient compliance, localisation, size and number of BrM, and outcome of extracranial disease. Generally, surgery or stereotactic radiotherapy followed by whole brain radiotherapy (WBRT) are indicated in patients with controlled extracranial disease and good performance status presenting an isolated BrM. Adding chemotherapy in this subset of patients is controversial. Supportive care associated with WBRT remains the standard treatment for all patients with multiple symptomatic BrM or with isolated symptomatic BrM in the presence of uncontrolled extracranial disease. For potentially chemosensitive patients with asymptomatic multiple or isolated BrM with disseminated disease, chemotherapy represents the optimal starting therapy.

Adenocarcinoma↗
PubMedDate not supplied

Metastatic spindle cell carcinoma: a complete response induced by cisplatin and 5-fluorouracil.

A patient with biopsy-proven spindle cell carcinoma, of unknown primary site, metastatic to the neck and to the lung, was treated with chemotherapy consisting of cisplatin (20 mg/m2/day) on days 1-5 and 5-fluorouracil (1000 mg/m2/day) on days 1-5. The regimen was repeated every 28 days. The patient had a complete response confirmed by computerized tomography. The patient is in a disease-free status 12 months after diagnosis. Toxicity was mild. To our knowledge, this case represents the first chemotherapy induced complete response documented in this rare entity.

Adult↗