Domenico Germano

Triplets versus doublets, with or without cisplatin, in the first-line treatment of stage IIIB–IV non-small cell lung cancer (NSCLC) patients: a multicenter randomised factorial trial (FAST)

Background:The FAST is a 2 × 2 factorial trial addressing two questions: (1) the role of replacing cisplatin (P) with a non-platinum agent, vinorelbine (N), and (2) the role of adding a third agent, ifosfamide (I), in a doublet based on gemcitabine (G).Methods:A total of 433 stage IIIB–IV non-small cell lung cancer (NSCLC) patients were randomised to one of four arms: gemcitabine–cisplatin (GP), gemcitabine–vinorelbine, gemcitabine–ifosfamide-cisplatin or gemcitabine–ifosfamide–vinorelbine. Two comparisons were performed: N- vs P-containing regimens and I-triplets vs non-I doublets.Results:For N- vs P-containing regimens, adjusted overall survival was 9.7 vs 11.3 months (P=0.044), progression-free survival was 4.9 vs 6.4 months (P=0.020) and response rate was 24% vs 31% (P=0.124), respectively. No statistically significant difference was observed between doublets and triplets. Grade 3–4 haematological toxicity was significantly more frequent in P-containing therapy; grade 3–4 leucopenia was significantly more common in triplets. Concerning non-haematological toxicity, grade 3–4 nausea-vomiting was significantly increased in P-containing regimens.Conclusions:This trial provides evidence of a slight survival superiority of GP-containing regimens over platinum-free N-containing chemotherapy. This trial also confirms that the addition of a third chemotherapy agent (I) to a standard G-based doublet does not improve treatment outcome.

Predictive Comprehensive Geriatric Assessment in elderly prostate cancer patients: the prospective observational scoop trial results

The Comprehensive Geriatric Assessment (CGA) represents the future of the geriatric oncology to reduce toxicities and treatment-related hospitalization in the elderly. Most patients receiving docetaxel for metastatic castration-resistant prostate cancer are in their seventies or older. We explored the efficacy of the CGA in predicting chemotherapy feasibility and response to docetaxel in a cohort of 24 patients aged at least 70. This was an observational, prospective study involving 24 patients who were 70 years of age or older and about to start chemotherapy with docetaxel for metastatic castration-resistant prostate cancer; we performed a CGA including five domains and divided our patients into ‘healthy’ and ‘frail’; the relations between general condition and (i) early chemotherapy discontinuation and (ii) response to docetaxel were explored. We found a statistically significant relationship between frailty assessed by CGA and early docetaxel discontinuation; we also found an association between frailty and response to chemotherapy, but this did not reach statistical significance. A geriatric assessment before starting chemotherapy may help clinicians to recognize frail patients, and hence to reduce toxicities and early treatment discontinuation. Further analyses are required to simplify the CGA tools and to facilitate its incorporation into routine clinical practice.

Scelte terapeutiche e trattamento con sorafenib nell’epatocarcinoma: analisi finale dello studio GIDEON in Italia

INTRODUCTION Sorafenib, an oral multikinase inhibitor, is the only targeted agent approved for the treatment of patients with hepatocellular carcinoma (HCC) after demonstration to increase overall survival compared to placebo in two randomized phase III study. GIDEON (Global Investigation of therapeutic DEcisions in HCC and Of its treatment with sorafeNib) is the largest, global, non-interventional, prospective study of patients with uHCC (n>3200) treated with sorafenib in real-life clinical practice conditions. Here we report the final analysis of safety and efficacy in the Italian cohort of patients. METHODS Patients with unresectable HCC who are candidates for systemic therapy, and for whom a decision has been made to treat with sorafenib, are eligible for inclusion. Patients demographics disease characteristics and treatment history were recorded at baseline visit. Sorafenib dose, concomitant medications, performance status, liver function, adverse events and efficacy (survival and response rate) were collected throughout the study. RESULTS In the Italian cohort of the GIDEON study 278 patients were included in 36 centers. The global rate of adverse events was 81%. Drug-related events accounted for 67%, mostly of grade 1 and 2, and only 8% were classified as serious. The most common were diarrhea (24%), fatigue (23%), dermatological (14%), rash/exfoliation (10%), hypertension (9%), hemorrage/bleeding of gastrointestinal tract (6%). Overall survival was 14.4 months and time to progression 6.2 months. Objective responses were observed in 14 patients (5%) with 3 complete responses (1%). Stable diseases of at least 6 weeks were observed in 113 patients (41%) with a 30% of disease control rate. DISCUSSION The safety profile of sorafenib in terms of rate and type of adverse events is similar to that emerged in the global international GIDEON study as well as in the pivotal registration studies.INTRODUCTION Sorafenib, an oral multikinase inhibitor, is the only targeted agent approved for the treatment of patients with hepatocellular carcinoma (HCC) after demonstration to increase overall survival compared to placebo in two randomized phase III study. GIDEON (Global Investigation of therapeutic DEcisions in HCC and Of its treatment with sorafeNib) is the largest, global, non-interventional, prospective study of patients with uHCC (n>3200) treated with sorafenib in real-life clinical practice conditions. Here we report the final analysis of safety and efficacy in the Italian cohort of patients. METHODS Patients with unresectable HCC who are candidates for systemic therapy, and for whom a decision has been made to treat with sorafenib, are eligible for inclusion. Patients demographics disease characteristics and treatment history were recorded at baseline visit. Sorafenib dose, concomitant medications, performance status, liver function, adverse events and efficacy (survival and response rate) were collected throughout the study. RESULTS In the Italian cohort of the GIDEON study 278 patients were included in 36 centers. The global rate of adverse events was 81%. Drug-related events accounted for 67%, mostly of grade 1 and 2, and only 8% were classified as serious. The most common were diarrhea (24%), fatigue (23%), dermatological (14%), rash/exfoliation (10%), hypertension (9%), hemorrage/bleeding of gastrointestinal tract (6%). Overall survival was 14.4 months and time to progression 6.2 months. Objective responses were observed in 14 patients (5%) with 3 complete responses (1%). Stable diseases of at least 6 weeks were observed in 113 patients (41%) with a 30% of disease control rate. DISCUSSION The safety profile of sorafenib in terms of rate and type of adverse events is similar to that emerged in the global international GIDEON study as well as in the pivotal registration studies.

Long-term survival in a patient with metastatic squamous cell lung carcinoma: A case report

Non-small-cell lung cancer (NSCLC) is the most common malignancy in industrialized countries, with a 5-year survival rate of only ~15%, as the majority of the patients have advanced-stage disease at diagnosis and the treatment options are limited. Squamous cell carcinoma the second most frequent type of NSCLC and is closely associated with cigarette smoking. We herein present the case of a 72-year-old male smoker, diagnosed with stage IV squamous cell lung carcinoma, with a solitary brain metastasis. After the diagnosis, stereotactic radiotherapy was performed on the brain metastasis. Following radiotherapy, chemotherapy with carboplatin + paclitaxel was initiated. However, after 2 cycles of chemotherapy, disease progression in the lung was observed. Therefore, second-line treatment with pemetrexed was started, which was discontinued after 2 cycles due to further disease progression. Third-line treatment with erlotinib was then administered, with notable benefit, as the patient remains alive after 6 years of treatment with a good performance status. The mutation status of EGFR was unknown.

A phase II trial of topotecan and ifosfamide in patients with previously treated, advanced non small cell lung carcinoma (NSCLC)

7314 Background: A number of second line treatments have been proposed in patients (pts) with advanced pretreated NSCLC. However, either single agents or two or three drug combinations achieved very poor results with no superiority of any combination over single agents. METHODS In this study we have treated 42 pts affected by advanced NSCLC previously submitted to chemotherapy (CT) with topotecan (1.2 mg/m2 ) plus ifosfamide (1,200 mg/m2) for 3 consecutive days every 3 weeks. The median age was 63 yrs with a range between 43 and 76; male/female ratio was 30/12; 14 pts had squamous carcinoma, 7 adenocarcinoma, 3 large cell, 2 broncho-alveolar carcinoma and 16 NSCLC not otherwise specified. All but one pts had previously received one CT regimen: 36 pts a cisplatinum based, 2 pts a carboplatin regimen and one pt an oxaliplatin based regimen. Moreover, one pt had previously received gemcitabine plus vinorelbine and one docetaxel alone as first line chemotherapy. The only naïve patient was included in the trial because of poor PS due to presence of brain metastases. The ECOG PS was 0 in 8 pts (19%), 1 in 11 pts (26%) and 2 in 23 pts (55%). The median number of courses administered was 3,3 (range 1-8). RESULTS Partial response (PR) was observed in 5/41 pretreated pts (12,2%) and in the naïve patient. In addition, one (2,4%) minimal (<50%) response (MR) plus 14 (34%) stable disease (SD) and 21(51%) progressive disease (PD) were observed. Grade 3-4 neutropenia was the dose limiting toxicity, observed in 36% of pts. Moreoveer, grade 3-4 anemia was observed in 17% and grade 3-4 thrombocytopenia in 12% of pts, respectively. One PS 2 patient died for grade 4 hematological toxicity after the first cycle. Median survival for the entire group was 26 weeks (range 1-91+) with 14% of pts alive at one yr. CONCLUSIONS In conclusion, the combination of topotecan and ifosfamide demonstrated antitumor activity with modest side effect profile in patients with previously treated NCSLC, with an overall disease control (PR+MR+SD) of 48.8%. Nevertheless, the still low response rate and the shortness of median survival claim for more effective second line treatments in this disease. No significant financial relationships to disclose.