Rituximab in steroid-refractory immune-related pancreatitis: a case report.

The use of immune checkpoint inhibitors (ICIs) for treating several types of cancer is increasing, but they may be associated with immune-related adverse events (irAEs). Pancreatitis is a rare irAE, mostly responsive to steroid treatment. There are no published data on the management of steroid-refractory ICI-induced pancreatitis. Rituximab has shown efficacy in the setting of relapsing non-ICI-induced autoimmune pancreatitis. However, its use has not been tested for treating immunotherapy-related pancreatitis. Here, we present the case of a patient with steroid-refractory immune-related pancreatitis successfully treated with rituximab as a potential strategy for irAE management.

Oncological outcomes of squamous cell carcinoma of the cervical esophagus treated with definitive (chemo-)radiotherapy: a systematic review and meta-analysis.

PURPOSE: To determine the oncological outcomes of cervical esophageal squamous cell carcinoma (CESCC) treated with definitive chemoradiotherapy (CRT). METHODS: A systematic review and meta-analysis was performed according to the PRISMA guidelines. RESULTS: A total of 1222 patients (median age: 63.0 years, 95% CI 61.0-65.0) were included from 22 studies. The median follow-up time was 34.0 months (n = 1181, 95% CI 26.4-36.0). Estimated pooled OS rates (95% CI) at 1, 3, and 5 years were 77.9% (73.9-82.2), 48.4% (43.2-54.3), and 35.3% (29.7-41.9), respectively. The median OS (95% CI) was 33.4 months (25.8-42.2). Estimated pooled PFS rates (n = 595; 95% CI) at 1, 3, and 5 years were 64.1% (57.9-71.0), 38.0% (33.3-45.5), and 29.8% (23.9-37.1), respectively. The median PFS (95% CI) was 19.8 months (14.9-26.6). CONCLUSIONS: Definitive CRT is a valuable first-line treatment for the management of CESCC. Further studies should focus on survival predictors able to define stage-based clinical guidelines.

Reply to Letter to the Editor regarding "Oncological outcomes of squamous cell carcinoma of the cervical esophagus treated with definitive (chemo-)radiotherapy: a systematic review and meta-analysis".

In a previous study, we performed a meta-analysis of the oncological outcomes of patients suffering from cervical esophageal squamous cell carcinoma treated with definitive chemoradiotherapy. Further analysis was performed, and a random effect modeling showed a pooled local-regional failure rate of 41.4% (95% CI 32.2-50.8), and a pooled distant failure rate of 21.6% (95% CI 17.0-26.5). The included studies used a median radiotherapy (RT) dose of 61.2 Gy (95% CI 60.0-62.0, range 56.0-66.0), but we measured a non-significant impact of the RT dose on the pooled overall survival (OS), suggesting that an increased RT dose might not be related to an improved OS (p = 0.23). Further research should be conducted to define predictors and prognostic categories that may select the best treatment option for each patient.

Oncological outcomes of cervical esophageal cancer treated primarily with surgery: a systematic review and meta-analysis.

PURPOSE: To determine the oncological outcomes of cervical esophageal cancer (CEC) treated primarily with surgery. METHODS: A systematic review and meta-analysis was performed according to the PRISMA guidelines. RESULTS: A total of 868 patients were included from 18 studies. Estimated pooled Overall Survival (OS) rates (95% Confidence Interval, CI) at 1 and 5 years were 74.4% (66.5-83.3), and 26.6% (20.3-34.7), respectively. Larynx non-preserving surgery (n = 229) showed an estimated pooled OS rates (95% CI) at 1 and 5 years of 59.3% (51.5-68.2) and 14.6% (8.8-24.3), respectively. On the other hand, larynx preserving surgery (n = 213) showed an estimated pooled OS rates (95% CI) at 1 and 5 years of 83.6% (78.2-89.4) and 35.1% (24.9-49.6), respectively. CONCLUSIONS: Primary larynx-preserving surgery remains a valuable option for the management of CEC, with similar survival outcomes compared to primary chemoradiotherapy (CRT). On the other hand, larynx non-preserving surgery showed a significantly reduced survival, that may reflect the more advanced T classification of these tumors. Further studies are mandatory to directly compare primary surgery and primary CRT, distinguishing larynx preserving and non-preserving surgery.

Quality of life of adult cancer survivors enrolled in Humanitas Research Hospital's survivorship care model.

INTRODUCTION: Clinicians should address the different health needs of cancer survivors (CS). We investigated concerns about physical/psychosocial symptoms and quality of life (QoL) of CS enrolled in our survivorship program. Our primary aim is to describe the CS population and their quality of life, considering both physical and psychosocial issues, with the intent to identify some possible association with the most frequently observed variables. METHODS: Adult patients, after ≥ 5 years from achieving complete hematologic or solid tumor remission, were included. The self-administered questionnaire used in the survey was based on the "Cancer Survivors Survey of Needs" (Mayo Clinic). RESULTS: We analyzed data from 191 CS. The median age was 63 years (53 years at diagnosis), and 70% of patients were females. A total of 93 patients (49%) reported a quality of life (QoL) score > 2. The most common psychosocial symptom concerns were fear of relapse (53%), genetic counseling (43%), living with uncertainty (35%), defining a new sense of normal (31%), and managing stress (28%). Females are more at risk to develop the following concerns compared with males: pain (40% vs 21%), sleep disturbance (54% vs 30%), weight gain (42% vs 21%), osteoporosis (41% vs 11%), body changes (45% vs 13%), hair or skincare issues (42% vs 16%), hot flashes (40% vs 11%), fear of recurrence (74% vs 54%), and living with a sense of uncertainty (53% vs 29%). Younger patients reported a higher score (> 2) for physical and psychological concerns compared with older patients. CONCLUSION: In this study, differences in physical and psychological symptoms/stressors among women and younger patients were identified. Female and younger patients appear to report physical and psychosocial concerns more frequently than other subgroups of patients. These observations should be validated and deepened in larger, prospective studies and considered during the long-term follow-up of these subgroups of patients.

The impact of cancer: An Italian descriptive study involving 500 long-term cancer survivors.

INTRODUCTION: The well-being and quality of life (QoL) of long-term cancer survivors may be affected, both positively and negatively, by psychosocial factors related to the experience of being a cancer patient. We investigated whether, in long-term cancer survivors, the psychosocial impacts of cancer associate with socio-demographic-clinical variables; whether, within the positive and negative dimensions taken separately, some impacts are more intense than others; and whether these impacts explain QoL. METHODS: Italian long-term cancer survivors (n = 500) completed the Impact of Cancer (IOC-V2) and Short Form 36 Health Survey (SF-36) questionnaires. RESULTS: The IOC-V2 negative impact score associated with gender, education, occupational status and health issues, whereas no association was found between the positive impact score and socio-demographic-clinical variables. Of the positive impacts, Altruism/Empathy was the highest (p < 0.001); Positive self-evaluation was higher than Health awareness (p = 0.001); and Meaning of cancer was the lowest (p < 0.001). Among the negative impacts, Worry was the highest (p < 0.001), whereas Body changes concerns was higher than both Appearance concerns (p < 0.001) and Life Interferences (p < 0.001). The assessed impacts explained more than 25% of the variance of both physical and mental functioning scores. CONCLUSIONS: The provided data document psychosocial factors affecting QoL in Italian long-term cancer survivors.

NGR-hTNF and Doxorubicin as Second-Line Treatment of Patients with Small Cell Lung Cancer.

LESSONS LEARNED: NGR-hTNF was safely combined with doxorubicin, showing a promising antitumor activity in unselected patients with relapsed small cell lung cancer.Similar antitumor activity was observed in platinum-sensitive and platinum-resistant patient cohorts. BACKGROUND: Relapsed small cell lung cancer (SCLC) patients have limited treatment options and poor outcomes. NGR-hTNF is a vascular-targeting agent, which increases intratumoral chemotherapy penetration and T-lymphocyte infiltration. METHODS: Twenty-eight patients relapsing after at least one platinum-based regimen with a treatment-free interval shorter (n = 16; platinum-resistant) or longer (n = 12; platinum-sensitive) than 3 months received NGR-hTNF 0.8 µg/m2 plus doxorubicin 75 mg/m2 every 3 weeks. The primary endpoint of this single-arm phase II trial was progression-free survival (PFS), and safety, response rate, and survival were secondary endpoints. RESULTS: The most common grade 3-4 toxicities were neutropenia (53%) and anemia (21%). Median PFS was 3.2 months for all patients, 2.7 months for platinum-resistant patients, and 4.1 months for platinum-sensitive patients. Seven patients had partial responses (25%), including four (25%) with platinum-resistant and three (25%) with platinum-sensitive relapse. Mean changes from baseline in tumor burden (after two, four, and six cycles) did not differ between platinum-resistant (-9%, -29%, and -32%) and platinum-sensitive (-11%, -20%, and -43%) cohorts. Overall survival was associated only with baseline lymphocyte counts, with median survival times of 13.1 and 5.2 months for lymphocyte counts above or below the median, respectively. CONCLUSION: NGR-hTNF plus doxorubicin showed manageable toxicity and promising activity in patients with relapsed SCLC.

Anthracycline-induced cardiotoxicity: A multicenter randomised trial comparing two strategies for guiding prevention with enalapril: The International CardioOncology Society-one trial.

BACKGROUND: Troponin changes over time have been suggested to allow for an early diagnosis of cardiac injury ensuing cancer chemotherapy; cancer patients with troponin elevation may benefit of therapy with enalapril. It is unknown whether a preventive treatment with enalapril may further increase the benefit. METHODS: The International CardioOncology Society-one trial (ICOS-ONE) was a controlled, open-label trial conducted in 21 Italian hospitals. Patients were randomly assigned to two strategies: enalapril in all patients started before chemotherapy (CT; 'prevention' arm), and enalapril started only in patients with an increase in troponin during or after CT ('troponin-triggered' arm). Troponin was assayed locally in 2596 blood samples, before and after each anthracycline-containing CT cycle and at each study visit; electrocardiogram and echocardiogram were done at baseline, and at 1, 3, 6 and 12-month follow-up. Primary outcome was the incidence of troponin elevation above the threshold. FINDINGS: Of the 273 patients, 88% were women, mean age 51 ± 12 years. The majority (76%) had breast cancer, 3% had a history of hypertension and 4% were diabetic. Epirubicin and doxorubicin were most commonly prescribed, with median cumulative doses of 360 [270-360] and 240 [240-240] mg/m2, respectively. The incidence of troponin elevation was 23% in the prevention and 26% in the troponin-triggered group (p = 0.50). Three patients (1.1%) -two in the prevention, one in the troponin-triggered group-developed cardiotoxicity, defined as 10% point reduction of LV ejection fraction, with values lower than 50%. INTERPRETATION: Low cumulative doses of anthracyclines in adult patients with low cardiovascular risk can raise troponins, without differences between the two strategies of giving enalapril. Considering a benefit of enalapril in the prevention of LV dysfunction, a troponin-triggered strategy may be more convenient.

Long-term quality of life profile in oncology: a comparison between cancer survivors and the general population.

PURPOSE: Understanding the quality of life (QoL) of cancer survivors is relevant to both clinical practice and health care policy. The current study compared the QoL profile in this specific population with that of a normative sample for the general population, as well as with those of both healthy and oncological patients normative sub-samples. In addition, associations between the obtained QoL profile and the main socio-demographic and clinical characteristics of the sample were examined. METHODS: Three hundred and ninety-two adult long-term cancer survivors (i.e., people 5 + years from their cancer diagnosis who were free from it and its treatments) were enrolled during follow-up visits and compiled the Short Form 36 Health Survey. RESULTS: In comparison with the normative data for the adult general population, the present sample showed lower scores in Physical functioning, Role-physical limitation, and Role-emotional limitations (all differences were both statistically and clinically significant); the difference in Vitality was only statistically significant. In all eight SF-36 scales, scores of the present sample were clinically and statistically lower than those of the normative healthy subsample, whereas they were statistically and clinically higher than those of normative subsample which had experienced cancer, except for Role-physical limitation. The QoL profile was associated with gender (p = 0.002), age (p = 0.001), education (p < 0.001), occupational status (p < 0.001), and the presence of other health issues (p < 0.001). CONCLUSION: These data support the utility of rehabilitative programs which integrate both healthcare and social interventions. In addition, they encourage the monitoring of the health status of this specific population, within a broad frame which simultaneously takes into consideration health and QoL.

Primary Debulking Surgery Versus Neoadjuvant Chemotherapy in Advanced Epithelial Ovarian Cancer: A Propensity-matched Analysis.

AIMS: To compare the surgical and survival outcomes of patients undergoing primary debulking surgery (PDS) versus neoadjuvant chemotherapy (NACT) plus interval debulking surgery (IDS) for advanced epithelial ovarian cancer (EOC). MATERIALS AND METHODS: Consecutive patients managed for advanced EOC since 2009 were matched through a propensity score analysis, defined as the probability of a woman having PDS or NACT plus IDS. RESULTS: The study group consisted of 100 propensity-matched women receiving PDS or NACT plus IDS. Groups resulted homogeneous in terms of baseline characteristics and pathologic findings. Patients undergoing PDS had longer operative time (P=0.032) and more blood loss (P=0.011) than the counterpart receiving NACT. No differences were found in terms of residual disease (P=0.11), as well as in terms of hospitalization, intraoperative, and postoperative complications. The mean progression-free survival was 23.0 and 27.7 months (P=0.67), whereas the overall survival (OS) was 44.5 and 43.2 months (P=0.48) for the PDS and NACT plus IDS group, respectively. Residual disease (P<0.0001) was the only independent predictor of progression-free and OS at multivariate analysis. CONCLUSIONS: PDS and NACT plus IDS achieved comparable results in terms of progression-free and OS in patients with advanced EOC.

Neoadjuvant Chemoradiotherapy with Volumetric-modulated Arc Therapy for Medium-distal Oesophageal and Gastro-oesophageal Junction Carcinoma.

AIM: to appraise the role of volumetric-modulated arc therapy (VMAT) in the neoadjuvant chemoradiotherapy management of advanced medium and distal oesophageal cancer in terms of toxicity and response to treatment. PATIENTS AND METHODS: Thirty patients were treated according to the neoadjuvant chemoradiation followed by surgery versus surgery-alone trial scheme with VMAT radiation therapy. Patients presented mainly T3-T4 stage (80%) and N1-2 (96.6%) disease. The chemotherapy scheme consisted of 3-5 cycles, while a radiotherapy course of 41.4 Gy in 23 fractions was administered to all patients. RESULTS: The median age of patients was 65 years, and there was a predominance of males (80%), smokers or ex-smokers (90%) and modest alcohol habit (80% negative). Primary tumor localisation was in the medium and distal third of the oesophagus in 57% of the cases, the rest being in the gastro-oesophageal junction. Modest toxicity profiles were observed, with limited incidence of grade 2-3 events. Partial or complete response was observed in more than 90% of the cases (radiological/metabolic) and was confirmed after surgical intervention (67% partial or complete and 27% stable response). Tumor down-staging was recorded in 67% of patients and nodal down-staging in 50%. CONCLUSION: VMAT was applied in the context of neoadjuvant chemoradiotherapy for the treatment of medium and distal oesophageal carcinoma with satisfactory results in terms of tolerance and toxicity.

Long-Term Follow-up Results of the DANTE Trial, a Randomized Study of Lung Cancer Screening with Spiral Computed Tomography.

RATIONALE: Screening for lung cancer with low-dose spiral computed tomography (LDCT) has been shown to reduce lung cancer mortality by 20% compared with screening with chest X-ray (CXR) in the National Lung Screening Trial, but uncertainty remains concerning the efficacy of LDCT screening in a community setting. OBJECTIVES: To explore the effect of LDCT screening on lung cancer mortality compared with no screening. Secondary endpoints included incidence, stage, and resectability rates. METHODS: Male smokers of 20+ pack-years, aged 60 to 74 years, underwent a baseline CXR and sputum cytology examination and received five screening rounds with LDCT or a yearly clinical review only in a randomized fashion. MEASUREMENTS AND MAIN RESULTS: A total of 1,264 subjects were enrolled in the LDCT arm and 1,186 in the control arm. Their median age was 64.0 years (interquartile range, 5), and median smoking exposure was 45.0 pack-years. The median follow-up was 8.35 years. One hundred four patients (8.23%) were diagnosed with lung cancer in the screening arm (66 by CT), 47 of whom (3.71%) had stage I disease; 72 control patients (6.07%) were diagnosed with lung cancer, with 16 (1.35%) being stage I cases. Lung cancer mortality was 543 per 100,000 person-years (95% confidence interval, 413-700) in the LDCT arm versus 544 per 100,000 person-years (95% CI, 410-709) in the control arm (hazard ratio, 0.993; 95% confidence interval, 0.688-1.433). CONCLUSIONS: Because of its limited statistical power, the results of the DANTE (Detection And screening of early lung cancer with Novel imaging TEchnology) trial do not allow us to make a definitive statement about the efficacy of LDCT screening. However, they underline the importance of obtaining additional data from randomized trials with intervention-free reference arms before the implementation of population screening.

Large volume unresectable locally advanced non-small cell lung cancer: acute toxicity and initial outcome results with rapid arc.

BACKGROUND: To report acute toxicity, initial outcome results and planning therapeutic parameters in radiation treatment of advanced lung cancer (stage III) with volumetric modulated arcs using RapidArc (RA). METHODS: Twenty-four consecutive patients were treated with RA. All showed locally advanced non-small cell lung cancer with stage IIIA-IIIB and with large volumes (GTV:299 ± 175 cm3, PTV:818 ± 206 cm3). Dose prescription was 66Gy in 33 fractions to mean PTV. Delivery was performed with two partial arcs with a 6 MV photon beam. RESULTS: From a dosimetric point of view, RA allowed us to respect most planning objectives on target volumes and organs at risk. In particular: for GTV D1% = 105.6 ± 1.7%, D99% = 96.7 ± 1.8%, D5%-D95% = 6.3 ± 1.4%; contra-lateral lung mean dose resulted in 13.7 ± 3.9Gy, for spinal cord D1% = 39.5 ± 4.0Gy, for heart V45Gy = 9.0 ± 7.0Gy, for esophagus D1% = 67.4 ± 2.2Gy. Delivery time was 133 ± 7s. At three months partial remission > 50% was observed in 56% of patients. Acute toxicities at 3 months showed 91% with grade 1 and 9% with grade 2 esophageal toxicity; 18% presented grade 1 and 9% with grade 2 pneumonia; no grade 3 acute toxicity was observed. The short follow-up does not allow assessment of local control and progression free survival. CONCLUSIONS: RA proved to be a safe and advantageous treatment modality for NSCLC with large volumes. Long term observation of patients is needed to assess outcome and late toxicity.

Multi-center phase II trial of chemo-radiotherapy with 5-fluorouracil, leucovorin and oxaliplatin in locally advanced esophageal cancer.

PURPOSE: The aim of this study was to evaluate the activity and safety of oxaliplatin/5-fluorouracil-based chemo-radiotherapy in patients with not radically resectable locally advanced esophageal cancer. METHODS: Fifty-nine patients with adeno or squamous-cell carcinoma received oxaliplatin (60 mg/m(2)), and leucovorin (20 mg/m(2) on days 1,8,15,29,36,43,50,57) followed by continuous infusion fluorouracil (200 mg/m(2) per day on days 1-22 and 29-64) with radiotherapy (1.8 Gy daily fractions to a total dose of 45 Gy, from days 29 to 64). When feasible, surgery was scheduled 6-8 weeks after chemo-radiotherapy completion. The primary endpoint was 1-year progression-free survival. RESULTS: Forty (68%) patients completed treatment without modifications. An objective clinical response was seen in 35 patients (59%). Esophagectomy was possible in 33 patients and a complete resection (R0) was achieved in 26 (79%) with 6 pathologic complete responses (pCR) and 3 near pCR. At a median follow-up of 39.7 months for the surviving patients, the median progression-free and overall survivals were 11 months (95% CI 6.5-14) and 18.5 months (95% CI 13-29). The 1-year progression-free and overall survivals were 47.5% (95% CI 34-59.5%) and 63% (95% CI 49-74%). Major toxicities were esophagitis (20% G3 and 5% G4) and diarrhea (8.5% G3 and 8.5% G4). Hematological toxicity (7% G3 and 3% G4) was less common; severe neurotoxicity (3% G3) was infrequent. CONCLUSIONS: Concurrent oxaliplatin, leucovorin, fluorouracil and radiotherapy followed or not by esophagectomy has a tolerable toxicity and promising activity in locally advanced esophageal cancer.

Gemcitabine and vinorelbine in pemetrexed-pretreated patients with malignant pleural mesothelioma.

BACKGROUND: Pemetrexed-cisplatin chemotherapy is the standard of care in the first-line treatment of unresectable malignant pleural mesothelioma (MPM). Second-line cytotoxic therapy is considered for a growing group of patients, but the optimal treatment has not been defined to date. Gemcitabine and vinorelbine have shown activity in the first-line setting. The objective of this study was to evaluate the activity and toxicity of the gemcitabine-vinorelbine combination in pemetrexed-pretreated patients with MPM. METHODS: From January 2004 to September 2006, 30 consecutive patients who were pretreated with pemetrexed with or without a platinum-derivative were enrolled. Gemcitabine 1000 mg/m(2) and vinorelbine 25 mg/m(2) were administered intravenously on Days 1 and 8 every 3 weeks. Treatment was repeated for a maximum of 6 cycles or until progression or unacceptable toxicity. RESULTS: A partial response was observed in 3 patients (10%; 95% confidence interval [CI], 2.1-26.5%), and 10 patients (33.3%; 95% CI, 17.3-52.8%) had stable disease after treatment. Overall, 13 patients (43.3%; 95% CI, 25.5-62.6%) achieved disease control. The median time to progression was 2.8 months (range, 0.6-12.1 months), and the median survival was 10.9 months (range, 0.8-25.3 months). Hematologic toxicity was acceptable, with grade 3 or 4 neutropenia occurring in 11% of patients and thrombocytopenia occurring in 4% of patients; no case of febrile neutropenia was observed. Nonhematologic toxicity generally was mild. CONCLUSIONS: The gemcitabine and vinorelbine combination was moderately active and had an acceptable toxicity profile in pemetrexed-pretreated patients with MPM. The role of second-line treatment in MPM needs to be evaluated in prospective trials in large series of patients who are stratified according to previous treatment and prognostic factors.

Pemetrexed single agent in previously treated non-small cell lung cancer: a multi-institutional observational study.

UNLABELLED: Several drugs have been approved for the treatment of patients affected by advanced non-small cell lung cancer (NSCLC) in progression after first line chemotherapy: Docetaxel, Pemetrexed and Erlotinib. Poor gain of survival has been demonstrated in randomised trials and patient characteristics predicting activity are poorly known yet. We evaluated the activity and toxicity of Pemetrexed, in a post-registration phase, to assess whether clinical benefits justify its employment in a second-line setting in routine clinical practice. PATIENTS AND METHODS: We collected data on patients with advanced NSCLC treated with Pemetrexed 500mg/m(2) every 21 days, after progression to prior chemotherapy. RESULTS: One hundred and sixty patients from 4 different Italian Institutions, treated with Pemetrexed, mostly as second-line therapy, were analysed. There was a predominance of males versus females, adenocarcinoma versus other histologies; the median age was 63.6 years. The toxicity profile was extremely mild and the response rate (11.2% patients in complete or partial response) was similar to previous reports from the literature. The median overall survival, 12 months, was better than previously reported. CONCLUSION: Improved efficacy and mild toxicity observed in this clinically relevant patient population confirms Pemetrexed as an interesting choice in second-line treatment of NSCLC. Patient characteristics alone are not able to predict response to Pemetrexed.

Assessment of tumor response in malignant pleural mesothelioma.

Most patients with malignant pleural mesothelioma (MPM) are candidates for chemotherapy during the course of their disease. Assessment of the response with conventional criteria based on computed tomography (CT) measurements is challenging, due to the circumferential and axial pattern of growth of MPM. Such difficulties hinder an accurate evaluation of clinical study results and make the clinical management of patients critical. Several radiological response systems have been proposed, but neither WHO criteria nor the more recent RECIST unidimensional criteria nor hybrid uni- and bidimensional criteria seem to apply to tumor measurement in this disease. Recently, modified RECIST criteria for MPM have been published. Although they are already being used in current clinical trials, they have been criticized based on the high grade of inter-observer variability and on theoretical studies of mesothelioma growth according to non-spherical models. Computer-assisted techniques for CT measurement are being developed. The use of FDG-PET for prediction of response and, more importantly, of survival outcomes of MPM patients is promising and warrants validation in large prospective series. New serum markers such as osteopontin and mesothelin-related proteins are under evaluation and in the future might play a role in assessing the response of MPM to treatment.

Phase II trial of alternating intravenous and oral vinorelbine in combination with cisplatin in advanced non-small cell lung cancer.

Cisplatin-based chemotherapy is the standard treatment for advanced non-small cell lung cancer (NSCLC). Several platinum-based doublets have been tested in phase II/III trials with equivalent results in terms of tumour response and survival. Our study was designed to evaluate activity, tolerability and convenience of alternating intravenous (i.v.) and oral vinorelbine in combination with cisplatin in advanced NSCLC. Forty chemo-naive patients with stage IV or relapsed unresectable disease and good performance status were enrolled to receive i.v. cisplatin 40 mg/m(2) on days 1 and 2 plus i.v. vinorelbine 25 mg/m(2) on day 1, every 3 weeks. Oral vinorelbine 60 mg/m(2) was given at home on day 5, without checking of blood cell count. A total of 175 treatment cycles were delivered. The overall response rate was 30% (one complete, 11 partial responses). Median time to progression and overall survival were 5 and 10 months, respectively. The main toxicity was haematological, with grade 3-4 neutropenia observed in 75% of patients, without febrile neutropenia. Non-haematological toxicity was mild. This schedule of cisplatin and vinorelbine treatment showed a good toxicity profile and an efficacy similar to other standard regimens. Oral vinorelbine could be administered safely at home on day 5.

Cisplatin plus gemcitabine on days 1 and 4 every 21 days for solid tumors: result of a dose-intensity study.

BACKGROUND: Three and 4-week cisplatin-gemcitabine schedules have shown similar dose-intensity (DI) and activity in non-small-cell lung cancer (NSCLC). The 3-week schedule is generally preferred because it enables better treatment compliance. To improve DI and compliance further, we delivered gemcitabine plus cisplatin over 4 days every 21 days. METHODS: Patients with any stage NSCLC or epithelial neoplasms and an ECOG PS < or = 2 were given gemcitabine 1000 mg/m(2) on days 1 and 4 plus cisplatin 70 mg/m(2) on day 2 of a 21-day cycle. Minimax design was used and a received DI for gemcitabine of > or = 580 mg/m(2)/wk was considered successful. RESULTS: Thirty-nine patients (34 NSCLC, 5 epithelial neoplasias) were enrolled. SWOG grade 3-4 neutropenia and thrombocytopenia were observed in 17.9% and 12.8% of patients, respectively. Nonhematological toxicity was minimal. Twenty-eight (18%) of 158 cycles required dose modifications and/or delays. Twenty-five patients received a gemcitabine dose intensity of > or = 580 mg/m(2)/wk. The received DIs were 601.8 mg/m(2)/wk for gemcitabine and 21.0 for cisplatin, with a relative DIs of 90.3% and 90.1%, respectively. The response rate of 27 evaluable patients with NSCLC was 44% (95% confidence interval [CI], 25.3 to 62.7%). CONCLUSIONS: The shorter schedule of gemcitabine on days 1 and 4 plus cisplatin on day 2 produces an effective DI and a toxicity profile comparable to that of weekly regimens.

Is gemcitabine cost effective in cancer treatment?

Gemcitabine is a novel pyrimidine nucleoside antimetabolite agent that is active, either as monotherapy or in association with other cytotoxic compounds, in pancreatic, ovarian, breast, bladder and non-small-cell lung cancer. The drug has an acceptable toxicity profile with myelosuppression being the most common adverse event. Pharmacoeconomic assessments have been performed in order to determine whether gemcitabine is a cost effective cancer treatment. Several cost analyses have investigated gemcitabine in association with cisplatin in the treatment of non-small-cell lung cancer, indicating that the combination is cost effective when compared with either old- or new-generation platinum-based treatments. Results in other malignancies are not corroborated by the same quality of evidence, therefore more extensive analyses are warranted. Overall, available data indicate that accurate selection of patients and careful cost analyses should be included in the development of new anticancer drugs for an appropriate use of limited healthcare resources.