Biological characterization and selection criteria of adjuvant chemotherapy for early breast cancer: experience from the Italian observational NEMESI study.

BACKGROUND: International treatment guidelines recommend administration of adjuvant chemotherapy in early breast cancer based on clinical, prognostic and predictive parameters. METHODS: An observational study (NEMESI) was conducted in 63 Italian oncology centres in patients with early breast cancer. Age, performance status, concomitant disease, menopausal status, histology, tumor dimension (pT), axillary lymph node status (pN), grading (G), estrogen and progesterone receptor (ER and PgR), proliferative index (ki67 or MIB-1), human epidermal growth factor receptor 2 (HER2) and type of adjuvant treatment were recorded. The primary objective of the study was to define parameters influencing the decision to prescribe adjuvant chemotherapy and the type of chemotherapy. RESULTS: Data for 1894 patients were available. 69.0% postmenopausal, 67.0% pT1, 22.3% pTmic/pT1a/pT1b, 61.0% pN0, 48.7% luminal A, 18.1% luminal B, 16.1% HER2 positive, 8.7% triple negative, 8.4% unknown. 57.8% received adjuvant chemotherapy: 38.1% of luminal A, 67.3% luminal B, 88.2% HER2-positive, 97.6% triple negative. Regimens administered: 9.1% CMF-like, 48.8% anthracyclines, 38.4% anthracyclines plus taxanes, 3.7% taxanes alone. Increasing pT/pN and, marginally, HER2-positive were associated with the prescription of anthracyclines plus taxanes. Suboptimal schedules (CMF-like or AC/EC or FEC-75) were prescribed in 37.3% receiving chemotherapy, even in HER2-positive and triple negative disease (36.5% and 34.0%, respectively). CONCLUSIONS: This study showed an overprescription of adjuvant chemotherapy for early breast cancer, particularly referred to luminal A. pT, pN and, marginally, HER2 were the principal determinants for the choice of chemotherapy type. Suboptimal chemotherapy regimens were adopted in at least one third of HER2-positive and triple negative.

Training young oncologists in doctor-patient relationships.

The importance of the doctor-patient relationship is not given adequate attention during the years of study leading to a degree in medicine. This aspect is important for all patients but especially so for cancer patients. What is the best way of training young doctors to overcome this problem?

[From treatment to palliative care: difficult news in oncology]. / Dal trattamento oncologico alle cure palliative: i momenti difficili della comunicazione.

The transition from oncological treatment to palliative care represents one of the most difficult moments in communicating bad news to patients. Even the most experienced doctor can feel profoundly affected when facing these moments.

Attitude of Italian medical oncologists toward palliative care for patients with advanced cancer: results of the SIO project.

PURPOSE: The aim of this survey was to describe the attitude of Italian oncologists towards palliative care. METHODS: A survey on palliative care was carried out among 400 Italian oncologists. RESULTS: Seventy-two percent indicated that the management of patients with advanced stage cancer represents the majority of their practice. They are often involved in the management of pain (78%) and complications of chemotherapy (61%), and frequently, in the treatment of terminal patients (60%). Only 8.5% reported having frequent collaboration with psychiatrists in support of emotional and psychological patients' disturbances. About 40% are often directly involved in the management of existential or spiritual distress. Discussions on euthanasia and assisted suicide, which are illegal in Italy, took place never (68%) or occasionally (27%). CONCLUSIONS: Respondents agreed that all oncology centres should have access to palliative care service. These results are in line with those of the European Society of Medical Oncology survey and may be usefully employed to improve the organisation of palliative care.

Association of high TUBB3 with resistance to adjuvant docetaxel-based chemotherapy in gastric cancer: translational study of ITACA-S.

BACKGROUND: No predictive markers for chemotherapy activity have been validated in gastric cancer (GC). The potential value of class III ß-tubulin (TUBB3) as biomarker for prognosis and resistance to taxane-based therapy was reported. METHODS: We analyzed GC samples of patients enrolled in the Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach (ITACA-S), a randomized adjuvant study comparing 5-fluorouracil/leucovorin (5-FU/LV) and docetaxel-based sequential chemotherapy. TUBB3 was quantitated by selected reaction monitoring mass spectrometry and patients were stratified using a threshold of 750 attomoles per microgram (amol/µg). Cox proportional modeling and Kaplan-Meier survival analysis were used to assess the impact of TUBB3 expression on overall survival (OS) and disease-free survival. RESULTS: Patients with TUBB3 protein levels >750 and <750 amol/µg were 21.9% and 78.1%, respectively, and were well-balanced between treatment arms. TUBB3 protein levels were not prognostic. Whereas no survival differences according to the 2 arms were observed in the subgroup with low TUBB3 expression (5-year OS 47% vs 40%; p = 0.44), patients with high TUBB3 had a clinically meaningful poorer OS when receiving docetaxel-based versus 5-FU/LV chemotherapy (5-year OS 31% vs 54%; p = 0.09), with a statistically significant interaction between TUBB3 and treatment (p = 0.049). CONCLUSIONS: The quantification of TUBB3 might be considered as a negative predictive biomarker of benefit from taxane-based therapy in GC. Studies are needed to evaluate its role in the neoadjuvant setting.

Sorafenib therapy for hepatocellular carcinoma in an HIV-HCV coinfected patient: a case report.

BACKGROUND/AIMS: HIV and hepatitis C virus (HCV) share common modes of transmission, resulting in about 33% incidence of coinfection among people infected with HIV. The survival benefit from highly effective antiretroviral therapy (HAART) for HIV infection is resulting in an increased incidence of hepatocellular carcinoma (HCC) in this population. There are no reports to date regarding the coadministration of HAART and sorafenib for hepatocellular carcinoma. METHODS: We report the case of a 42-year-old male patient coinfected with HIV and HCV who developed advanced HCC not amenable to curative therapy. The patient was treated with sorafenib, an oral multikinase inhibitor shown to lead to a longer median survival time and time to progression in patients with advanced HCC. Antiretroviral therapy was continued during sorafenib therapy. RESULTS: The patient achieved a partial tumor response after 3 months and continued to respond at subsequent assessments. His serum alpha-fetoprotein normalized from 2,172 IU/ml to 2 IU/ml. He had durable stable disease after 23 months of therapy. Antiretroviral therapy was efficacious (CD4(+) lymphocyte count, 377/microl; HIV viremia, <50 copies/ml). The simultaneous administration of these therapies was well tolerated. No grade 3 or 4 toxicities were observed. Exacerbation of pre-existing hypertension, grade 2 diarrhea, and grade 1 skin reaction were observed. CONCLUSIONS: This is the first report in which sorafenib has been successfully used to treat HCC in a patient with HIV-HCV coinfection.

Weekly docetaxel vs. docetaxel-based combination chemotherapy as second-line treatment of advanced non-small-cell lung cancer patients. The DISTAL-2 randomized trial.

BACKGROUND: Doublet chemotherapy is more effective than single-agent as first line treatment of advanced non-small-cell lung cancer (NSCLC). No reliable information instead is available on the effect of doublets in second line treatment. The aim of DISTAL-2 study was to compare two doublets containing docetaxel with single agent docetaxel as second line treatment of patients with NSCLC (ClinicalTrials.gov id.:.NCT00345059). METHODS: NSCLC patients, aged <75, PS 0-2, who had failed platinum-based chemotherapy, were randomly assigned with a 3:1:1 ratio to: arm A, weekly docetaxel (33.3mg/m(2) on days 1, 8, 15 q 4 weeks); arm B, weekly docetaxel (30 mg/m(2) on days 1, 8, 15) plus gemcitabine (800 mg/m(2) on days 1, 8 q 4 weeks) or plus vinorelbine (20mg/m(2) on days 1, 8 q 4 weeks) depending on which of the two had been used in first line; arm C, weekly docetaxel (as in arm B) plus capecitabine (625 mg/m(2) twice daily on days 5-18 q 4 weeks). Primary end-point was overall survival (OS). Two comparisons were planned: arm B vs. A and arm C vs. A. Overall, 375 patients had to be randomized. Response was assessed by RECIST, quality of life (QoL) by EORTC questionnaires. RESULTS: 84 patients were randomized from May 2005 to December 2006, when the trial was prematurely stopped due to the slow accrual. After 62 deaths, median OS was 40.0 weeks in arm A, 32.6 weeks in arm B (p=0.18 vs. A) and 39.7 weeks in arm C (p=0.90 vs. A). Response rate was 6.4, 16.7 and 5.3%, and median progression-free survival was 12.4, 13.1 and 11.9 weeks, for arms A, B and C, respectively. Patients in arm B had significantly more grade 3-4 haematological and non-haematological toxicity compared to arm A, and patients in arm C had significantly more grade 3-4 non-haematological toxicity compared to arm A. No relevant differences were found in QoL analysis, with the exception of significant worsening in appetite, vomiting and hemoptysis for patients in arm B. CONCLUSION: Due to early termination, the trial does not have the planned statistical power. However, available data do not support the role of docetaxel-based combination chemotherapy as second line in advanced NSCLC.

Cetuximab plus gemcitabine and cisplatin compared with gemcitabine and cisplatin alone in patients with advanced pancreatic cancer: a randomised, multicentre, phase II trial.

BACKGROUND: Preclinical data have suggested a synergistic effect of cetuximab combined with gemcitabine and cisplatin and clinical data have shown a substantial improvement in response and survival when gemcitabine is combined with a platinum analogue compared with gemcitabine alone. The aim of this study was to assess the activity and feasibility of a combination of cetuximab with gemcitabine and cisplatin compared with use of gemcitabine and cisplatin alone for the treatment of advanced pancreatic cancer. METHODS: In a multicentre, randomised phase II trial, 84 patients with advanced pancreatic cancer were randomly assigned to either 250 mg/m2 cetuximab weekly, after a loading dose of 400 mg/m2, plus 1000 mg/m2 gemcitabine and 35 mg/m2 cisplatin on days 1 and 8 of a 21-day cycle or to the same chemotherapeutic regimen without cetuximab. The primary endpoint was objective response (defined as the proportion of patients whose best response was either partial response or complete response). Secondary endpoints included disease control (defined as the proportion of patients whose best response was either partial response, complete response, or stable disease), progression-free survival, and overall survival. All assessments of response at each site were done blindly by a local experienced radiologist who was not directly involved in the trial. Responses were measured according to an intention-to-treat analysis. This trial is registered with the Clinical Trial registry, number NCT00536614. FINDINGS: 29 men and 13 women were randomly assigned to cetuximab plus gemcitabine and cisplatin (median age 61 years [range 38-78]) and 22 men and 20 women were randomly assigned to gemcitabine and cisplatin (median age 64 years [range 40-76]). Seven of 40 (17.5%) patients had an objective response in the cetuximab group (95% CI 7.3-32.8) and five of 41 (12.2%) patients had an objective response in the non-cetuximab group (95% CI 4.1-26.2). No significant difference was noted between the groups both for objective response (5.3% higher in the cetuximab group [95% CI -16.5 to 27.1]; chi2 test=0.360; p=0.549) or for disease control (3.5% higher in the non-cetuximab group [-34.0% to 27.0%]; 0.446; p=0.504). Overall median follow-up was 11.8 months (range 2.5-18.5). No significant differences between the groups were noted in median progression-free survival (hazard ratio 0.96, 95% CI 0.60-1.52, p=0.847) or in median overall survival (0.91, 0.54-1.55, p=0.739): median progression-free survival was 3.4 months (95% CI 2.4-5.1) in the cetuximab group and 4.2 months (2.6-5.4) in the non-cetuximab group; median overall survival was 7.5 months (5.1-8.8) and 7.8 months (5.3-15.0), respectively. 33 patients from both groups had at least one grade 3-4 toxic effect. INTERPRETATION: The addition of cetuximab to a combination of gemcitabine and cisplatin does not increase response or survival for patients with advanced pancreatic cancer. Although toxic effects were not increased by cetuximab, this combination should not be further assessed in phase III trials.

Oxycodone controlled-release as first-choice therapy for moderate-to-severe cancer pain in Italian patients: results of an open-label, multicentre, observational study.

BACKGROUND AND OBJECTIVES: Cancer pain affects patients at all stages of the disease and there are clear guidelines for its management. Morphine is considered the first-choice strong opioid in the treatment of moderate-to-severe pain; however, numerous studies have shown that oxycodone controlled-release (CR) has a similar efficacy and safety profile. The purpose of this study was to evaluate the efficacy and tolerability of oxycodone CR as a first-line strong opioid for the treatment of moderate-to-severe pain in Italian cancer patients. METHODS: This was a prospective, open-label, multicentre, observational trial carried out at 15 locations across Italy. Patients with a referral for cancer-related pain of > or =5 on a 10-point numerical rating scale were enrolled. Patients were treated with oral oxycodone CR and monitored for 21 days. Dosage was individualized for each patient and up-titrated until effective pain control was achieved. Pain, adverse events and quality-of-life scores were assessed throughout the study. RESULTS: 390 patients (174 females and 216 males) with a mean age of 66 +/- 11 years were evaluated. The average daily dose ranged from 22.84 on day 1 to 40 mg/day on day 21. Pain intensity (assessed on a 10-point numerical rating scale) decreased significantly within 1 day of treatment commencement (p = 0.00001) and continued to decrease throughout the study period (from a mean 7.22 at baseline to a mean 2.11 points on day 21). Adverse events were mild to moderate in intensity and consisted of common opioid-related events. Ten patients (2.6%) discontinued the study because of adverse events and four (1%) because of uncontrolled pain. All aspects of activities of daily life assessed were improved by study end. CONCLUSIONS: Oxycodone CR is efficacious and well tolerated as a first-line strong opioid for the treatment of moderate-to-severe cancer-related pain in Italian patients.

Early mortality in myeloma patients treated with first-generation novel agents thalidomide, lenalidomide, bortezomib at diagnosis: A pooled analysis.

INTRODUCTION: Early toxic death (≤60 days of diagnosis) in elderly multiple myeloma (MM) patients is attributable to active disease, age and co-morbidities. Rate of early toxic deaths is 10% with conventional chemotherapy mainly due to infection and renal failure. Novel agents have improved MM outcome at the expense of newer toxicity. METHODS: We analyzed 1146 individual patient data to assess toxic deaths during induction treatment with first-generation novel agents thalidomide, lenalidomide, bortezomib. RESULTS: During first-line therapy, 119/1146 patients (10%) died for any cause, and 47/1146 (4%) due to toxicity, including 12/1146 (1%) early deaths. The 24-month cumulative incidence was 4.1% without any difference between bortezomib (18/503 patients, 4%) and lenalidomide (29/643patients, 5%; p = 0.31). Toxic deaths occurred in 34/1039 (3%) patients <80 years and 13/107 (12%) patients ≥80 years. Causes were cardiac events (28%), infections (26%) and vascular complications (15%). In a multivariate analysis, older age and unfavorable ISS stage increased the risk of death. CONCLUSION: First-generation novel agents significantly reduced toxic deaths compared to conventional chemotherapy. One third of deaths during first-line therapy were due to cumulative drug-related toxicities, thus supportive approaches and prevention strategies should be optimized. The higher mortality rate for toxicity in octogenarians confirms the need for a careful frailty assessment.

Primary pulmonary high grade non-Hodgkin's lymphoma in an elderly patient. A case report.

An 82-year-old non-smoker female was admitted with cough, fever and poor general health. Radiological examination revealed a right parahilar mass and a transbronchial biopsy confirmed the presence of a tumor. Immunohistochemical analysis established the diagnosis of high-grade primary pulmonary lymphoma. The rare nature of this disease, its non-specific clinical presentation and particular prognosis, also in elderly patients, are discussed in this article.

Anxiety levels in cancer patients and "life sound" experience.

AIMS AND BACKGROUND: For the hospitalized cancer patient, time takes on a rhythm which is very different from the external reality. Based on the idea that time represents a fundamental dimension of human existence and is connected to future plans, time spent waiting and memories, we carried out this experience entitled "Life Sound" project. The objectives of the project were to experiment different and unusual ways of spending time in hospital in order to improve the quality of life of the hospitalized cancer patient, to help the patient adapt to the hospital environment, to encourage awareness of self and to give a different meaning to time spent in the hospital. In particular, we evaluated the reduction in the levels of anxiety, in psychological suffering and the improvement in communication. METHODS: We met with patients, family members, friends, volunteers and department personnel (doctors, psychologists, nurses) in a room in the Oncology and Hematology Department set aside specifically for recreation activities such as having a cup of tea while listening to music, talking, joking, listening to people's memories and celebrating birthdays, anniversaries and other special days. The study, which involved 109 patients, was carried out through the use of the questionnaire STAI-Y distributed before and after the event. RESULTS: The results showed a statistically significant difference in anxiety levels 2 hrs before participation (mean = 38.33) and 2 hrs after participation (mean = 34.77) in the program. This variation was also assessed based on gender, age, cancer stage, time since diagnosis and performance status but did not result in any statistically significant difference. CONCLUSIONS: The "Life Sound" project encourages the emergence of positive feelings, of a renewed willingness to invest in personal and caring relationships, which are connected to the patient's ability to face this illness, and the opening of new channels of communication with family members and hospital staff.

Feasibility of sequential therapy with FOLFIRI followed by docetaxel/cisplatin in patients with radically resected gastric adenocarcinoma. A randomized phase III trial.

OBJECTIVE: Combination therapies of fluorouracil (FU) with irinotecan (CPT-11) and docetaxel plus cisplatin have been proven to be active in metastatic gastric cancer. In this paper, we present the results of a phase III trial in which these two combinations given sequentially were compared to mitomycin C (MMC) monochemotherapy in an adjuvant setting. METHODS: 169 patients with radically resected gastric cancer were randomized to receive CPT-11 (180 mg/m2 day 1), leucovorin (100 mg/m2 days 1-2), FU (400-600 mg/m2 days 1-2, q 14; for four cycles; FOLFIRI regimen), followed by docetaxel (85 mg/m2 day 1), cisplatin (75 mg/m2 day 1, q 21; for three cycles; arm A), or MMC (8 mg/m2 days 1-2 as 2-hour infusion, q 42; for four cycles; arm B). All patients had histologically confirmed gastric carcinoma with nodal positivity or pT3/4. A total of 166 patients (85 in arm A and 81 in arm B) were treated. Adjuvant treatment was completed in 76% of the patients in arm A and in 70% of the patients in arm B. The main grade 3/4 side effects recorded were neutropenia in 35%, with only 1 febrile patient, and diarrhea in 11% in arm A, and thrombocytopenia in 10% and neutropenia in 7% in arm B. The FOLFIRI regimen and docetaxel/cisplatin given in sequence was well tolerated and feasible in adjuvant setting. This sequence treatment currently represents the experimental arm of an ongoing multicenter trial.

That tumor you're going to get tomorrow maybe: making an informed decision.

With the recent progress in predictive medicine several problems have emerged regarding the ethical aspects of genetic testing. The role of the doctor in communicating the consequences of such testing to the patient has become more important than ever in allowing the potential patient to make an informed decision.

FOLFIRINOX-based neoadjuvant therapy in borderline resectable or unresectable pancreatic cancer: a meta-analytical review of published studies.

OBJECTIVE: The use of neoadjuvant chemotherapy can enable surgical resection of borderline resectable or unresectable pancreatic cancer (PC). The aim of this study was to evaluate the effectiveness of the multiagent 5-fluorouracil + oxaliplatin + irinotecan + leucovorin (FOLFIRINOX) regimen as a neoadjuvant treatment for PC. METHODS: Studies in which FOLFIRINOX with or without radiotherapy was given before surgery to patients with borderline resectable or unresectable PC were analyzed using a meta-analytical approach. The primary outcomes were resection rate and radical (R0) resection rate. Data were expressed as weighted pooled proportions with 95% confidence intervals (CIs). RESULTS: Thirteen studies, with a total of 253 patients, were included in this meta-analysis. After undergoing the treatment, 43% (95% CI, 32.8-53.8) of patients were resected and 39.4% (95% CI, 32.4-46.9) underwent R0 resection (85% of surgical specimens). In particular, among borderline resectable PCs, R0 resection was possible in 63.5% (95% CI, 49%-76%) of the cases. The rate of R0 resection in unresectable PCs was 22.5% (95% CI, 13.3-35.4). CONCLUSIONS: This meta-analysis shows that down-staging after neoadjuvant FOLFIRINOX-based therapy is noticeable in patients with borderline resectable/unresectable PC, with a total R0 resection rate of 40%.

Capecitabine, oxaliplatin and irinotecan in combination, with bevacizumab (COI-B regimen) as first-line treatment of patients with advanced colorectal cancer. An Italian Trials of Medical Oncology phase II study.

BACKGROUND: A dose-finding phase I/II trial that evaluated the maximum tolerated doses of a combination of three drugs with irinotecan, oxaliplatin and capecitabine (COI regimen) has been conducted in patients with metastatic colorectal cancer (mCRC). In this study the safety and activity of the combination of COI regimen plus bevacizumab (COI-B) were assessed. METHODS: Patients judged to be unresectable for metastatic disease, were enrolled in a phase II, open-label study and treated with the combination of bevacizumab (5mg/kg on day 1) and COI regimen (irinotecan 180mg/mq on day 1, oxaliplatin 85mg/mq on day 2, capecitabine 2000mg d2-6; q14) as first-line treatment. Induction treatment was administered for a maximum of 8 cycles, followed by maintenance treatment with bevacizumab (7.5mg/kg on d1, q21) until progression. RESULTS: Fifty-one patients were enrolled in six Italian centres. The primary end-point of overall response rate was met, reaching the value of 62% in the per-protocol population and 57% in the intent-to-treat population, patients with stable disease were also taken into account, the clinical benefit rate was 94%. In the intention-to-treat population, median progression-free and overall survivals were 10.3 and 22 months, respectively. Toxicity was different from 5-fluorouracil-based triplet regimens, with 31% of severe diarrhoea, but a low incidence of grade 3/4 neutropenia (6%) and mucositis (4%). CONCLUSIONS: Our results show the feasibility and promising activity of the combination of capecitabine, oxaliplatin, irinotecan and bevacizumab.

The value of lactate dehydrogenase serum levels as a prognostic and predictive factor for advanced pancreatic cancer patients receiving sorafenib.

Although lactate dehydrogenase (LDH) serum levels, indirect markers of angiogenesis, are associated with a worse outcome in several tumours, their prognostic value is not defined in pancreatic cancer. Moreover, high levels are associated even with a lack of efficacy of tyrosine kinase inhibitors, contributing to explain negative results in clinical trials. We assessed the role of LDH in advanced pancreatic cancer receiving sorafenib. Seventy-one of 114 patients included in the randomised phase II trial MAPS (chemotherapy plus or not sorafenib) and with available serum LDH levels, were included in this analysis. Patients were categorized according to serum LDH levels (LDH ≤ vs.> upper normal rate). A significant difference was found in progression free survival (PFS) and in overall survival (OS) between patients with LDH values under or above the cut-off (PFS: 5.2 vs. 2.7 months, p = 0.0287; OS: 10.7 vs. 5.9 months, p = 0.0021). After stratification according to LDH serum levels and sorafenib treatment, patients with low LDH serum levels treated with sorafenib showed an advantage in PFS (p = 0.05) and OS (p = 0.0012). LDH appears to be a reliable parameter to assess the prognosis of advanced pancreatic cancer patients, and it may be a predictive parameter to select patients candidate to receive sorafenib.

Gemcitabine and oxaliplatin: a safe and active regimen in poor prognosis advanced non-small cell lung cancer patients.

BACKGROUND AND AIMS: Most patients with non-small cell lung cancer (NSCLC) cannot tolerate a cisplatin-based chemotherapy because of old age, general conditions, and/or multiorgan metastatic sites. Oxaliplatin is active in NSCLC, offers advantage in terms of toxicity, and shows synergism with gemcitabine. The aims of this phase II study were to evaluate the response rate and toxicity of the gemcitabine-oxaliplatin combination in patients with advanced NSCLC and poor prognosis. METHODS: Patients were given a gemcitabine infusion (1000 mg/m(2) over 30 min on days 1 and 8) followed by oxaliplatin (65 mg/m(2) over 120 min on days 1 and 8) every 21 days for six cycles. RESULTS: Thirty-two patients with poor-prognosis advanced NSCLC received 136 cycles. There were 25 males and seven females, and the median age was 65 years (range 29-76). Fifty-six percent of patients had adenocarcinoma, and 31% had squamous cell carcinoma. Sixty-six percent of patients had stage IV disease, and 34% had stage IIIB disease. Eastern cooperative oncology group (ECOG) performance status was 2-3 in 50%, 1 in 44%, and 0 in 6% of patients. Eight patients (25%) had been previously treated with cisplatin or carboplatin. All patients were symptomatic. Of the 32 patients who received study drug, five (16%) achieved partial response, six (19%) had minor response, three (9%) had stable disease, and 15 (47%) progressed. The median overall survival was 27 weeks. Thirty-one patients were evaluable for toxicity: seven patients (23%) had grade 3-4 thrombocytopenia with no bleeding; four patients (13%) had grade 3-4 neutropenia with no febrile neutropenia, and three patients (10%) had grade 3 anemia. Two patients (6%) had grade 3, and six patients (19%) had grade 1-2 neurotoxicity. CONCLUSION: The combination of gemcitabine and oxaliplatin seems to be well tolerated and active in patients with poor prognosis advanced NSCLC and deserves further evaluation in phase II clinical trials.

Sorafenib does not improve efficacy of chemotherapy in advanced pancreatic cancer: A GISCAD randomized phase II study.

BACKGROUND: The RAF-MEK-ERK pathway is commonly activated in pancreatic cancer because of a high frequency of KRAS-BRAF mutations. A phase II randomized trial was designed to investigate the activity of sorafenib in combination with chemotherapy in advanced pancreatic cancer. METHODS: Locally advanced or metastatic pancreatic adenocarcinoma patients were randomized in a 1:1 ratio to receive cisplatin plus gemcitabine with sorafenib 400mg bid (arm A) or without sorafenib (arm B). RESULTS: One hundred and fourteen patients were enrolled; of these, 43 (74.6%) patients progressed in arm A and 44 (82.4%) in arm B. Median progression-free survival was 4.3 months (95% CI: 2.7-6.5) and 4.5 months (95% CI: 2.5-5.2), respectively (HR=0.92; 95% CI: 0.62-1.35). Median overall survival was 7.5 (95% CI: 5.6-9.7) and 8.3 months (95% CI: 6.2-8.7), respectively (HR=0.95; 95% CI: 0.62-1.48). Response rates were 3.4% in arm A and 3.6% in arm B. CONCLUSIONS: Sorafenib does not significantly enhance activity of chemotherapy in advanced pancreatic cancer patients, and therefore should not be assessed in phase III trials.