Impact of anemia management with EPO on psychologic distress in cancer patients: results of a multicenter patient survey.

AIM: We investigated the role of erythropoietin (EPO) in reducing anemia and preventing the development of psychological distress in patients treated with chemotherapy. PATIENTS & METHODS: This prospective observational study enrolled 591 adult patients receiving EPO at a dose of 30,000 IU administered once weekly for chemotherapy-induced anemia (mean baseline hemoglobin [Hb] level was 9.55 g/dl) over a 12-month period. RESULTS: The majority of patients (371 [71%] patients) achieved a Hb increase >2 g/dl after 4 weeks of treatment. Interestingly, the nonresponder group had a statistically significant deterioration of their psychological conditions as indicated by psychological distress score (p = 0.01). However, within the group of responders to EPO, the Psychological Distress Inventory score remained unchanged. In the present study, severe side effects associated with EPO were not recorded. CONCLUSION: Hb increase, induced by EPO, ameliorates the psychological conditions of cancer patients.

Cetuximab plus FOLFOX-4 in untreated patients with advanced colorectal cancer: a Gruppo Oncologico dell'Italia Meridionale Multicenter phase II study.

OBJECTIVES: FOLFOX-4 and FOLFIRI are considered equivalent in terms of activity and efficacy as first-line chemotherapy in metastatic colorectal cancer (mCRC). The monoclonal antibody (mAb) cetuximab showed intrinsic activity as a single agent in mCRC and was approved in combination with CPT-11 for patients who failed previous CPT-11-based treatment. The purpose of this phase II study was to evaluate the activity and safety of FOLFOX-4 plus cetuximab in untreated mCRC patients. METHODS: Untreated patients with measurable metastatic disease and expressing epidermal growth factor receptor (EGFR) received cetuximab at a loading dose of 400 mg/m(2), followed by weekly doses of 250 mg/m(2), in combination with the FOLFOX-4 regimen every 2 weeks for a maximum of 12 cycles, after which a maintenance program using cetuximab alone was allowed for a maximum of 6 months. RESULTS: Eighty-two unselected patients were screened; 70 were EGFR+ and entered the trial. Of the 67 assessable patients, the objective response rate was 64.2% (95% CI: 52.5-75.5%) and the tumor growth control rate was 94% (95% CI: 88-99%). All the objective responses except 1 were confirmed. In the group of patients with initially unresectable liver disease alone, 7/33 (21%) were resected. The median time to progression (TTP) and overall survival (OS) were 10.0 and 22.0 months, respectively. The treatment was well tolerated, with no treatment-related deaths, while 24.2% of the patients were affected by cutaneous toxicity of grade >2. Mutational analysis of the KRAS and BRAF genes was retrospectively performed on 35 of the 69 patients treated with cetuximab (51%). KRAS was mutated in 13 out of the 35 cases (37%), whereas no mutations were detected in the BRAF gene. A trend toward an association between KRAS mutations and objective response to treatment (p = 0.07) was demonstrated. Analysis of survival showed that patients harboring KRAS mutations had a trend toward worst TTP (p = 0.14) confirmed by age- and sex-adjusted Cox multivariate regression (hazard ratio, HR = 0.62; 95% CI: 0.36-1.06; p = 0.08). Indeed, KRAS mutations were significantly associated with worst OS in both unadjusted analysis (p = 0.047; log rank test) and age- and sex-adjusted Cox multivariate regression (HR = 0.458; 95% CI: 0.248-0.847; p = 0.01). CONCLUSIONS: These results suggest that the combination of FOLFOX-4 plus cetuximab is very active and obtains long TTP with an acceptable toxicity profile. Indeed, our results are in line with recent findings from phase II and phase III randomized studies providing strong evidence that the efficacy of anti-EGFR mAb is confined to patients with wild-type KRAS mCRC. Investigation of other predictive biomarkers may be useful to further define the responder population.

Activity of chemotherapy in mucinous ovarian cancer with a recurrence free interval of more than 6 months: results from the SOCRATES retrospective study.

BACKGROUND: Mucinous ovarian carcinoma have a poorer prognosis compared with other histological subtypes. The aim of this study was to evaluate, retrospectively, the activity of chemotherapy in patients with platinum sensitive recurrent mucinous ovarian cancer. METHODS: The SOCRATES study retrospectively assessed the pattern of care of a cohort of patients with recurrent platinum-sensitive ovarian cancer observed in the years 2000-2002 in 37 Italian centres. Data were collected between April and September 2005. Patients with recurrent ovarian cancer with > 6 months of platinum free interval were considered eligible. RESULTS: Twenty patients with mucinous histotype and 388 patients with other histotypes were analyzed. At baseline, mucinous tumours differed from the others for an higher number of patients with lower tumor grading (p = 0.0056) and less advanced FIGO stage (p = 0.025). At time of recurrence, a statistically significant difference was found in performance status (worse in mucinous, p = 0.024). About 20% of patients underwent secondary cytoreduction in both groups, but a lower number of patients were optimally debulked in the mucinous group (p = 0.03). Patients with mucinous cancer received more frequently single agent platinum than platinum based-combination therapy or other non-platinum schedules as second line therapy (p = 0.026), with a response rate lower than in non-mucinous group (36.4% vs 62.6%, respectively, p = 0.04). Median time to progression and overall survival were worse for mucinous ovarian cancer. Finally, mucinous cancer received a lower number of chemotherapy lines (p = 0.0023). CONCLUSION: This analysis shows that platinum sensitive mucinous ovarian cancer has a poor response to chemotherapy. Studies dedicated to this histological subgroup are needed.

Chemotherapy with gemcitabine and oxaliplatin in patients with advanced biliary tract cancer: a single-institution experience.

BACKGROUND: Biliary tract cancers are uncommon tumors with a poor prognosis. Since most patients present with invasive and inoperable disease at diagnosis, treatment consists of palliative chemotherapy, with poor response rates and a median survival of less than 6 months. Oxaliplatin and gemcitabine have shown interesting activity as single agents in this patient group. OBJECTIVE: A single-institution phase II study was performed to evaluate the efficacy and safety of combination therapy with oxaliplatin and gemcitabine in locally advanced and metastatic biliary tract carcinomas. PATIENTS AND METHODS: Combination chemotherapy consisted of gemcitabine 1,000 mg/m(2) on day 1 and oxaliplatin 100 mg/m(2) on day 2 every 2 weeks. Treatment was administered until disease progression, unacceptable toxicity or patient refusal. Thirty-five consecutive patients with advanced biliary tract carcinoma, aged 18-80 years, with Eastern Cooperative Oncology Group performance status < or =2 were entered into our study from November 2003. RESULTS: Thirty- four patients were evaluable for response and toxicity. According to RECIST criteria, 2 patients had a complete response and 12 had a partial response, with an overall response rate of 41%. Overall survival in our patients was 10 months (range 2-30). According to WHO criteria, 3 patients (9%) suffered from grade 3 neutropenia and 7 patients (21%) from grade 3 thrombocytopenia. Only 3 patients (9%) had grade 3 neuropathy. CONCLUSIONS: The GEMOX combination seems to be active with a favorable safety profile in first-line chemotherapy of advanced biliary tract cancers.

An adrenal gland nodule presenting as an early sign of metastatic spread from colorectal cancer: report of two cases.

The presence of an adrenal gland nodule may be an early or late sign of metastatic spread from colorectal cancer. It usually appears when the internal malignancy is widely disseminated and has been previously diagnosed. Adrenal insufficiency can be compatible with bilateral and diffuse involvement of this uncommon site of disease. Although a surgical approach can be proposed in some circumstances, chemotherapy is usually the only therapeutic option. We present 2 cases that document examples of both events, so as to illustrate the most relevant aspects of this condition.

Phase III randomized trial of FOLFIRI versus FOLFOX4 in the treatment of advanced colorectal cancer: a multicenter study of the Gruppo Oncologico Dell'Italia Meridionale.

PURPOSE: We performed this phase III study to compare the irinotecan, leucovorin (LV), and fluorouracil (FU) regimen (FOLFIRI) versus the oxaliplatin, LV, and FU regimen (FOLFOX4) in previously untreated patients with advanced colorectal cancer. PATIENTS AND METHODS: A total of 360 chemotherapy-naive patients were randomly assigned to receive, every 2 weeks, either arm A (FOLFIRI: irinotecan 180 mg/m(2) on day 1 with LV 100 mg/m(2) administered as a 2-hour infusion before FU 400 mg/m(2) administered as an intravenous bolus injection, and FU 600 mg/m(2) as a 22-hour infusion immediately after FU bolus injection on days 1 and 2 [LV5FU2]) or arm B (FOLFOX4: oxaliplatin 85 mg/m(2) on day 1 with LV5FU2 regimen). RESULTS: One hundred sixty-four and 172 patients were assessable in arm A and B, respectively. Overall response rates (ORR) were 31% in arm A (95% CI, 24.6% to 38.3%) and 34% in arm B (95% CI, 27.2% to 41.5%; P = .60). In both arms A and B, median time to progression (TTP; 7 v 7 months, respectively), duration of response (9 v 10 months, respectively), and overall survival (OS; 14 v 15 months, respectively) were similar, without any statistically significant difference. Toxicity was mild in both groups: alopecia and gastrointestinal disturbances were the most common toxicities in arm A; thrombocytopenia and neurosensorial were the most common toxicities in arm B. Grade 3 to 4 toxicities were uncommon in both arms, and no statistical significant difference was observed. CONCLUSION: There is no difference in ORR, TTP, and OS for patients treated with the FOLFIRI or FOLFOX4 regimen. Both therapies seemed effective as first-line treatment in these patients. The difference between these two combination therapies is mainly in the toxicity profile.

Pretreatment quality of life and functional status assessment significantly predict survival of elderly patients with advanced non-small-cell lung cancer receiving chemotherapy: a prognostic analysis of the multicenter Italian lung cancer in the elderly study.

PURPOSE: To study the prognostic value for overall survival of baseline assessment of functional status, comorbidity, and quality of life (QoL) in elderly patients with advanced non-small-cell lung cancer treated with chemotherapy. PATIENTS AND METHODS: Data from 566 patients enrolled onto the phase III randomized Multicenter Italian Lung Cancer in the Elderly Study (MILES) study were analyzed. Functional status was measured as activities of daily living (ADL) and instrumental ADL (IADL). The presence of comorbidity was assessed with a checklist of 33 items; items 29 and 30 of the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 (EORTC QLQ-C30) were used to estimate QoL. ADL was dichotomized as none versus one or more dependency. For IADL and QoL, three categories were defined using first and third quartiles as cut points. Comorbidity was summarized using the Charlson scale. Analysis was performed by Cox model, and stratified by treatment arm. RESULTS: Better values of baseline QoL (P = .0003) and IADL (P = .04) were significantly associated with better prognosis, whereas ADL (P = .44) and Charlson score (P = .66) had no prognostic value. Performance status 2 (P = .006) and a higher number of metastatic sites (P = .02) also predicted shorter overall survival. CONCLUSIONS: Pretreatment global QoL and IADL scores, but not ADL and comorbidity, have significant prognostic value for survival of elderly patients with advanced non-small-cell lung cancer who were treated with chemotherapy. Using these scores in clinical practice might improve prognostic prediction for treatment planning.

Extending the platinum-free interval with a non-platinum therapy in platinum-sensitive recurrent ovarian cancer. Results from the SOCRATES Retrospective Study.

BACKGROUND: It has been proposed that extending the platinum-free interval with intervening non-platinum therapy increases the efficacy of a later re-treatment with platinum in platinum-sensitive recurrent ovarian cancer. This hypothesis is based on data from small series and although it has not been validated prospectively, this strategy has entered general practice in Italy in the last years. The SOCRATES study retrospectively assessed the pattern of care of a cohort of patients with recurrent platinum-sensitive ovarian cancer observed in the years 2000-2002 in 37 Italian centres. Data were collected between April and September 2005. METHODS: Patients with recurrent ovarian cancer with a platinum-free interval >6 months were eligible. 493 patient files were collected and 428 were eligible and analyzed. RESULTS: The interval from the end of the 1st line to relapse was 6-12 months in 164 patients (39.5%) and >12 months in 251 cases (60.5%). Patients received a 2nd (100%), 3rd (80.1%), 4th (50.2%), 5th (28.3%), and 6th (11.9%) line of chemotherapy. At 2nd line 282 (65.9%) received platinum (group A), while 146 (34.1%) received non-platinum chemotherapy (group B). In the latter group, 67 patients received platinum at later progression (group B1), while 79 never received platinum (group B2). Median time to platinum re-treatment was 20 and 23.1 months in patients of groups A and B1, respectively. The response rate to the first platinum received was 74.4 and 57.4% in groups A and B1, respectively (p = 0.02). Group B2 was characterized by the worst response rate and survival. At multivariate analysis time of first platinum re-treatment (2nd line vs. later; p = 0.0132; OR = 2.34) and age (p = 0.0029; OR = 2.41) was independently associated with a higher possibility of response to platinum. CONCLUSIONS: With the limits of a retrospective study, our data question the hypothesis that extending the platinum-free interval with an intervening non-platinum therapy in patients with recurrent platinum-sensitive ovarian cancer improves the response rate of a further platinum re-treatment.

Residual neurotoxicity in ovarian cancer patients in clinical remission after first-line chemotherapy with carboplatin and paclitaxel: the Multicenter Italian Trial in Ovarian cancer (MITO-4) retrospective study.

BACKGROUND: Carboplatin/paclitaxel is the chemotherapy of choice for advanced ovarian cancer, both in first line and in platinum-sensitive recurrence. Although a significant proportion of patients have some neurotoxicity during treatment, the long-term outcome of chemotherapy-induced neuropathy has been scantly studied. We retrospectively assessed the prevalence of residual neuropathy in a cohort of patients in clinical remission after first-line carboplatin/paclitaxel for advanced ovarian cancer. METHODS: 120 patients have been included in this study (101 participating in a multicentre phase III trial evaluating the efficacy of consolidation treatment with topotecan, and 19 treated at the National Cancer Institute of Naples after the end of the trial). All patients received carboplatin (AUC 5) plus paclitaxel (175 mg/m2) every 3 weeks for 6 cycles, completing treatment between 1998 and 2003. Data were collected between May and September 2004. Residual sensory and motor neurotoxicity were coded according to the National Cancer Institute--Common Toxicity Criteria. RESULTS: 55 patients (46%) did not experience any grade of neurological toxicity during chemotherapy and of these none had signs of neuropathy during follow-up. The other 65 patients (54%) had chemotherapy-induced neurotoxicity during treatment and follow-up data are available for 60 of them. Fourteen out of 60 patients (23%) referred residual neuropathy at the most recent follow-up visit, after a median follow up of 18 months (range, 7-58 months): 12 patients had grade 1 and 2 patients grade 2 peripheral sensory neuropathy; 3 patients also had grade 1 motor neuropathy. The remaining 46/60 patients (77%) had no residual neuropathy at the moment of interview: recovery from neurotoxicity had occurred in the first 2 months after the end of chemotherapy in 22 (37%), between 2 and 6 months in 15 (25%), or after more than 6 months in 9 patients (15%). Considering all 120 treated patients, there was a 15% probability of persistent neurological toxicity 6 months after the end of chemotherapy. CONCLUSION: A significant proportion of patients with advanced ovarian cancer treated with first-line carboplatin/paclitaxel suffer long-term residual neuropathy. This issue should be carefully taken into account before considering re-treatment with the same agents in sensitive recurrent disease.

Gemcitabine plus vinorelbine compared with cisplatin plus vinorelbine or cisplatin plus gemcitabine for advanced non-small-cell lung cancer: a phase III trial of the Italian GEMVIN Investigators and the National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: Platinum-containing chemotherapy regimens are the standard treatment for patients with advanced non-small-cell lung cancer (NSCLC), although toxicity is common and may significantly affect the patient's quality of life (QoL). This trial aimed to assess whether a combination of gemcitabine and vinorelbine had benefits in terms of QoL, without influencing negatively on survival, compared with cisplatin-containing regimens. PATIENTS AND METHODS: Patients with stage IIIB (effusion and supraclavicular nodes) or IV documented NSCLC who were younger than 70 years of age were randomly assigned gemcitabine plus vinorelbine (GemVin) or either gemcitabine plus cisplatin or vinorelbine plus cisplatin (cisplatin-based). European Organization for Research and Treatment of Cancer scales were used for QoL analysis. RESULTS: Five hundred one patients were randomly assigned to treatment. The median age was 62 years. There were no significant differences in global QoL scores between the two arms after 2 months of treatment. However, worsening scores for appetite, vomiting, and alopecia were significantly more common in the cisplatin-based arm. Median survival was 38 v 32 weeks and median progression-free survival was 23 v 17 weeks in the cisplatin-based versus GemVin arms, respectively. For the GemVin arm the hazard ratio for death was 1.15 (90% confidence interval [CI], 0.96 to 1.37) and the hazard ratio for progression was 1.29 (90% CI, 1.10 to 1.52). Grade 3 or 4 myelosuppression, vomiting, alopecia, and ototoxicity were significantly more frequent with cisplatin-based treatment. CONCLUSION: Global QoL is not improved with GemVin, although advantages in some components of QoL were apparent. GemVin is less toxic than standard cisplatin-based chemotherapy. There is a nonsignificant slight survival advantage with cisplatin-based chemotherapy. GemVin could be offered to advanced NSCLC patients who express concern about toxicity.

Topotecan compared with no therapy after response to surgery and carboplatin/paclitaxel in patients with ovarian cancer: Multicenter Italian Trials in Ovarian Cancer (MITO-1) randomized study.

PURPOSE: Topotecan is an active second-line treatment for advanced ovarian cancer. Its efficacy as consolidation treatment after first-line standard chemotherapy is unknown. PATIENTS AND METHODS: To investigate whether topotecan (1.5 mg/m(2) on days 1 through 5, four cycles, every 3 weeks) prolonged progression-free survival (PFS) for patients responding to standard carboplatin (area under the curve 5) and paclitaxel (175 mg/m(2) administered as a 3-hour infusion in six cycles; CP), a multicenter phase III study was performed with an 80% power to detect a 50% prolongation of median PFS. Patients were registered at diagnosis and randomized after the end of CP. RESULTS: Two hundred seventy-three patients were randomly assigned (topotecan, n = 137; observation, n = 136), with a median age of 56 years. Stage at diagnosis was advanced in three fourths of patients (stage III in 65% of patients; stage IV in 10%); after primary surgery, 46% had no residual disease and 20% were optimally debulked. After CP, 87% reached a clinical complete response, and 13% achieved a partial response. Neutropenia (grade 3/4 in 58% of the patients) and thrombocytopenia (grade 3 in 21%; grade 4 in 3%) were the most frequent toxicities attributed to topotecan. There was no statistically significant difference in PFS between the arms (P =.83; log-rank test): median PFS was 18.2 months in the topotecan arm and 28.4 in the control arm. Hazard ratio of progression for patients receiving topotecan was 1.18 (95% CI, 0.86 to 1.63) after adjustment for residual disease, interval debulking surgery, and response to CP. CONCLUSION: The present analysis indicates that consolidation with topotecan does not improve PFS for patients with advanced ovarian cancer who respond to initial chemotherapy with carboplatin and paclitaxel.

Carboplatin in combination with raltitrexed in recurrent and metastatic head and neck squamous cell carcinoma: A multicentre phase II study of the Gruppo Oncologico Dell'Italia Meridionale (G.O.I.M.).

BACKGROUND: The combination of cisplatin (CDDP) and 5-Fluorouracil (5-FU) is a standard regimen for the treatment of recurrent and metastatic head and neck squamous cell carcinoma (HNSCC). This combination shows a relevant toxicity and new chemotherapy associations with a more favourable toxicity profile are awaited. Carboplatin (CB) is a platinum derivative with less toxicity than CDDP. Raltitrexed (R) is a potent and specific thymidylate synthase inhibitor with activity comparable to that of 5-FU in colorectal cancer; moreover, it showed activity as a single agent in HNSCC. MATERIALS AND METHODS: Since 2001, a multicentre, phase II trial has been underway to evaluate the efficacy and toxicity of the CB+R combination in untreated patients with recurrent or metastatic HNSCC. Thirty-two patients were enrolled and included in an intent-to-treat analysis. Toxicity was graded according to NCI criteria. Patients had a histo/cytologically proven recurrent or metastatic HNSCC; patients with locally advanced disease not amenable to CDDP+5-FU treatment were also included. Patients had to be >18 years old with ECOG PS of 0-2 and adequate bone marrow, renal and liver functions. CB (AUC 5) and R (3 mg/m2) were administered intravenously every 3 weeks. The median age was 62 years (range 43-71), 29 M/3 F. The median PS was 1 (0-2). Twelve patients were staged III and 20 were metastatic (10 recurrent). The oral cavity/oropharynx were the primary site in 20 patients and the larynx in 10 patients. The median number of cycles delivered was 3, while globally 115 cycles were administered. The median time to progression was 4.2 months and median duration of survival was 9.8 months. RESULTS: Seven patients achieved a partial response (22%), 10 patients showed a stable disease (31%), while 13 patients (48%) had progressive disease. Eight patients (25%) had a G 3-4 neutropenia, while G 3-4 anaemia was observed in 2 patients and thrombocytopenia in 1 patient. No extrar haematological G 3-4 toxicities were observed. A persistent G 2 hepatic toxicity led a patient to drop out from the study. CONCLUSION: In our phase II trial, CB in combination with R showed a moderate activity with safe administration on an outpatient basis.

Raltitrexed and mitomycin-C as third-line chemotherapy for colorectal cancer after combination regimens including 5-fluorouracil, irinotecan and oxaliplatin: a phase II study.

BACKGROUND: To investigate the therapeutic value and safety of a third-line treatment with raltitrexed and mitomycin-C (MMC) in patients with advanced colorectal cancer (ACC) pretreated with combination regimens including 5-fluorouracil (5-FU), irinotecan (CPT-11) and oxaliplatin (L-OHP). PATIENTS AND METHODS: A total of 21 patients (PS 1/2, 19/2; M/F 15/6; median age = 73) with ACC, all of whom had developed progressive disease while receiving or within 6 months of discontinuing two sequential chemotherapy lines with 5-FU, CPT-11 and L-OHP, were accrued in this study. At the time of their relapse, cytotoxic chemotherapy, consisting of intravenous raltitrexed 3 mg/m2 plus MMC 6 mg/m2 on therapeutic day 1, was initiated. Treatment courses were repeated every 4 weeks for a total of six courses unless there was prior evidence of progressive disease, unacceptable toxicity or patient refusal occurred. RESULTS: All the patients were assessable for toxicity and 16 for response evaluation, having completed at least two courses of chemotherapy. The overall response rate was 0%. Seven patients (33.6%) had a stable disease and nine patients (43%) progressed. The median time to progression was 2.3 months (95% CI: 1.65-2.95%) and median overall survival (OS) 5 months (95% CI: 2.52-7.48%). No toxic deaths occurred. Third-line treatment tolerance was generally mild to moderate and easy to treat. WHO grade 3/4 anemia, neutro- and thrombocytopenia occurred in 9.5%, 4.7% and 4.7% of the patients, respectively. However, these toxicities did not have a significant impact on global quality of life. CONCLUSION: Our data suggest that the association of raltitrexed and MMC in patients with ACC pretreated with combination regimens including 5-FU, CPT-11 and L-OHP is feasible and could contribute to increase patients' OS time. Further evaluation of this regimen seems to be warranted.

Single agent vinorelbine as first-line chemotherapy in elderly patients with advanced breast cancer.

BACKGROUND: Breast cancer arises in about 48% of patients (pts) older than 65 years. Chemotherapy is administered to elderly pts with advanced breast cancer (ABC) resistant to hormonal treatment or with visceral metastases. Vinorelbine (VNR), a semisynthetic vinca alkaloid, is active and well-tolerated in ABC reporting, as a single agent, an objective response (OR) rate of 41%-60%. The ELVIS (Elderly Lung cancer Vinorelbine Italian Study) trial demonstrated the tolerability and efficacy of VNR in elderly pts with advanced non-small cell lung cancer (JNCI 91: 66-72, 1999). MATERIALS AND METHODS: From January 1999 to December 2000, we analysed, retrospectively, our data about single-agent VNR as a first-line chemotherapy in elderly pts (> or = 70 years) with ABC. Twenty-four pts were analysed. VNR was administered at the dose of 30 mg/m2, i.v., days 1 and 8, every 3 weeks for a maximum of 6 cycles. RESULTS: The main toxicity was (% of pts): grade (G) 3-4 neutropenia 25%; G 2 thrombocytopenia 4.1%; G 2 asthenia 25%; G 2-3 constipation 16.6%; and G 1 neurotoxicity 25%. No cycles of chemotherapy were omitted or postponed. Granulocyte colony-stimulating factor was administered in 12.5% of a total of 112 cycles. Nine (37.5%) objective responses (2 complete and 7 partial responses) were observed. The median duration of response and survival were 7 and 11 months, respectively. CONCLUSION: These results suggest that single agent VNR is active and well-tolerated in elderly pts with ABC. Further prospective trials are warranted.

Responsiveness of skin metastases to CMF in a patient with urothelial carcinoma of the bladder: a case report.

Skin metastases from urothelial carcinoma of the bladder are uncommon, and there are few cases reported in literature. The present case report describes the results of a combination of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) administered as second-line chemotherapy in a cisplatin-resistant metastatic bladder cancer patient. The improvement in cutaneous lesions and pain reduction obtained prompt further exploration of the activity of this regimen in a second-line approach.

The impact of anemia on quality of life and hospitalisation in elderly cancer patients undergoing chemotherapy.

AIM OF THE STUDY: at present, there is very little data available about the impact of anemia on elderly cancer patient's quality of life (QoL). Most of the acquired knowledge has been derived from small studies selected for primary site cancer. This observational study investigates the association between hemoglobin (Hb) level and comprehensive geriatric assessment variables: Cancer Linear Analog Scale (CLAS), Activities of Daily Living (ADL), Mini-Mental State Examination (MMSE) in elderly cancer patients undergoing chemotherapy (CT). METHODS: we enrolled 586 elderly cancer patients undergoing CT who were evaluated at baseline and every 3-4 weeks for at least 12 weeks. The correlation between Hb level changes and the examined index changes were performed using Pearson correlation analysis and a multivariate analysis was performed using a logistic regression model. RESULTS: both univariate and multivariate analyses at baseline showed that Hb values are related to ECOG performance status (PS), stage of disease and self-reported QoL. Hb level variation significantly correlated with CLAS and ADL changes measured at baseline and after 12 weeks. This correlation is highly significant in patients with Hb< 11g/dl. Multivariate analysis showed that Hb change of at least 1g/dl was the only independent predictor of a better quality of life, when assessed by using the CLAS and ADL questionnaire (p<0.05). Moreover the median time of hospitalisation was found to be significantly lower in patients showing higher Hb level (Hb ≥ 11g/dl) (p=0.037). CONCLUSIONS: the findings of this study seem to provide adequate support for the correlation between anemia and elderly cancer patient's QoL. Interestingly, we reported an association between anemia and the length of hospitalisation in this setting of patients. However, the above results do need to be confirmed by further prospective trials.

Randomized phase III trial of gemcitabine plus cisplatin compared with single-agent gemcitabine as first-line treatment of patients with advanced pancreatic cancer: the GIP-1 study.

PURPOSE: Single-agent gemcitabine became standard first-line treatment for advanced pancreatic cancer after demonstration of superiority compared with fluorouracil. The Gruppo Italiano Pancreas 1 randomized phase III trial aimed to compare gemcitabine plus cisplatin versus gemcitabine alone (ClinicalTrials.gov ID NCT00813696). PATIENTS AND METHODS: Patients with locally advanced or metastatic pancreatic cancer, age 18 to 75 years, and Karnofsky performance status (KPS) > or = 50, were randomly assigned to receive gemcitabine (arm A) or gemcitabine plus cisplatin (arm B). Arm A: gemcitabine 1,000 mg/m(2) weekly for 7 weeks, and, after a 1-week rest, on days 1, 8, and 15 every 4 weeks. Arm B: cisplatin 25 mg/m(2) added weekly to gemcitabine, except cycle 1 day 22. Primary end point was overall survival. To have 8% power of detecting a 0.74 hazard ratio (HR) of death, with bilateral alpha .05, 355 events were needed and 400 patients planned. RESULTS: Four hundred patients were enrolled (arm A: 199; arm B: 201). Median age was 63, 59% were male, 84% had stage IV, and 83% had KPS > or = 80. Median overall survival was 8.3 months versus 7.2 months in arm A and B, respectively (HR, 1.10; 95% CI, 0.89 to 1.35; P = .38). Median progression-free survival was 3.9 months versus 3.8 months in arm A and B, respectively (HR, 0.97; 95% CI, 0.80 to 1.19; P = .80). The objective response rate was 10.1% in A and 12.9% in B (P = .37). Clinical benefit was experienced by 23.0% in A and 15.1% in B (P = .057). Combination therapy produced more hematologic toxicity, without relevant differences in nonhematologic toxicity. CONCLUSION: The addition of weekly cisplatin to gemcitabine failed to demonstrate any improvement as first-line treatment of advanced pancreatic cancer.

New perspectives in the treatment of advanced or metastatic gastric cancer.

Metastatic gastric cancer remains an incurable disease, with a relative 5-year survival rate of 7%-27%. Chemotherapy, which improves overall survival (OS) and quality of life, is the main treatment option. Meta-analysis has demonstrated that the best survival results obtained in earlier randomized studies were achieved with three-drug regimens containing a fluoropyrimidine, an anthracycline, and cisplatin (ECF). Although there has been little progress in improving median OS times beyond the 9-mo plateau achievable with the standard regimens, the availability of newer agents has provided some measure of optimism. A number of new combinations incorporating docetaxel, oxaliplatin, capecitabine, and S-1 have been explored in randomized trials. Some combinations, such as epirubicin-oxaliplatin-capecitabine, have been shown to be as effective as (or perhaps more effective than) ECF, and promising early data have been derived for S-1 in combination with cisplatin. One factor that might contribute to extending median OS is the advancement whenever possible to second-line cytotoxic treatments. However, the biggest hope for significant survival advances in the near future would be the combination of new targeted biological agents with existing chemotherapy first-line regimens.

Gemcitabine and paclitaxel every 2 weeks in patients with previously untreated urothelial carcinoma.

BACKGROUND: Patients with urothelial carcinoma are not always amenable to cisplatin-based chemotherapy. The authors previously reported that they achieved a 60% response rate in patients who failed on cisplatin-based combination chemotherapy (methotrexate, vinblastine, doxorubicin, and cisplatin) by using a convenient outpatient regimen of gemcitabine (G) and paclitaxel (P) every 2 weeks. A multicenter trial was initiated in 5 Italian centers to evaluate this regimen as first-line chemotherapy. METHODS: From January 2003 to April 2005, 54 patients who had histologically proven, measurable disease (according to Response Evaluation Criteria in Solid Tumors) with a World Health Organization (WHO) performance status (PS) from 0 to 2, metastatic or inoperable urothelial carcinoma, no prior systemic cytotoxic or biologic treatment, a creatinine clearance >or=40 mL per minute, and bilirubin <20 micromol/L received G at a dose of 2500 mg/m(2) in 30 minutes and P at a dose of 150 mg/m(2) in 3 hours every 2 weeks. Granulocyte-colony-stimulating factor (G-CSF) was given for 5 to 7 days for neutropenia toxicity of grade >or=3 (grading determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 guidelines). From 6 to 12 courses were planned. All patients received at least 1 cycle of therapy and were included in all analyses. RESULTS: The median patient age was 67 years (range 34-78 years), and the median WHO PS was 1 (range, 0-2). Metastases occurred in the lung in 17 patients (31%), in lymph nodes in 26 patients (54%), in the bladder in 20 patients (37%), in bone in 8 patients (15%), and in the liver in 8 patients (15%). Fifty-nine percent of patients had >1 site of disease, and 13% of patients had >or=3 sites of disease. In total, 343 cycles were administered. Five patients achieved a complete response, and 15 patients achieved a partial response; thus, the overall response rate was 37% in an intent-to-treat analysis. Hematologic toxicity was predominant but manageable. G-CSF was used in only 6% of cycles. The median survival was 13.2 months, and the median time to disease progression was 5.8 months. CONCLUSIONS: In a multicenter study, G and P was found to be a well-tolerated outpatient regimen. This regimen demonstrated promise and may be considered in patients who are unable to receive cisplatin.