Trabectedin plus pegylated liposomal doxorubicin (PLD) versus PLD in recurrent ovarian cancer: Overall survival analysis

AimTrabectedin in combination with pegylated liposomal doxorubicin (PLD) improves progression-free survival (PFS) compared to PLD alone in recurrent ovarian cancer (J Clin Oncol 2010;28:3107–14).MethodsWomen, stratified by performance status (0–1 versus 2) and platinum sensitivity (platinum-free interval [PFI] <6 versus ⩾6 months), were randomly assigned to receive PLD 30 mg/m² IV followed by a 3-h infusion of trabectedin 1.1 mg/m² every 3 weeks or PLD 50 mg/m² every 4 weeks. The study was powered to show a 33% increase in overall survival (OS) after 520 deaths had occurred.ResultsAfter a median follow-up of 47.4 months, there were 522 deaths among 672 subjects. The median OS for trabectedin + PLD and PLD arms was 22.2 and 18.9 months, respectively (hazard ratio [HR] = 0.86; 95% confidence interval [CI]: 0.72–1.02; p = 0.0835). An unexpected but significant imbalance in the PFI favouring the PLD arm (mean PFI: PLD = 13.3 months, trabectedin + PLD = 10.6 months) was identified. On the basis of this finding, an unplanned hypothesis generating analysis adjusting for the PFI imbalance and other prognostic factors suggested an improvement in OS associated with the trabectedin + PLD arm (HR = 0.82; 95% CI: 0.69–0.98; p = 0.0285). In another unplanned exploratory analysis, the subset of patients with a PFI of 6–12 months had the largest difference in OS (HR = 0.64; 95% CI: 0.47–0.86; p = 0.0027).ConclusionsThe final OS analysis did not meet the protocol-defined criterion for statistical significance. Despite stratification on platinum sensitivity, there was an imbalance in mean platinum free interval that had an effect on OS.     

The risk of skin rash and stomatitis with the mammalian target of rapamycin inhibitor temsirolimus: a systematic review of the literature and meta-analysis

ObjectiveWe conducted a systematic review of the literature and performed a meta-analysis to determine the risk of developing skin rash and stomatitis among patients receiving temsirolimus.MethodsDatabases from PubMed and Web of Science from January, 1998 until June, 2011 and abstracts presented at the American Society of Clinical Oncology annual meetings from 2004 through 2011 were searched to identify relevant studies. The incidence and relative risk (RR) of skin rash and stomatitis were calculated using random-effects or fixed-effects model depending on the heterogeneity of included studies.ResultsA total of 779 patients from 10 clinical trials were included in this analysis. The overall incidence of all-grade rash was 45.8% (95% confidence interval (CI): 35.6–56.3%), with a RR of 7.6 (95% CI: 4.4–13.3; p < 0.001). The overall incidence of high-grade rash was 3.3% (95% CI: 1.9–5.6%), with a RR of 13.70 (95% CI: 0.82–227.50, p = 0.07). The overall incidence of all-grade stomatitis was 44.3% (CI: 32.1–57.1%), with a RR of 11.10, 95% CI: 5.60–22.00; p < 0.001). The overall incidence of high-grade stomatitis was 3.2% (95% CI: 1.9–5.4%), with a RR of 13.2 (95% CI: 0.80–218.50, p = 0.07).ConclusionThere is a significant risk of developing skin rash and stomatitis in cancer patients receiving temsirolimus. The risk is independent of underlying tumour. Adequate monitoring and early intervention are recommended to prevent debilitating toxicity and suboptimal dosing.     

Induction chemotherapy followed by gefitinib and concurrent thoracic radiotherapy for unresectable locally advanced adenocarcinoma of the lung: a multicenter feasibility study (JCOG 0402)

BackgroundWe conducted a feasibility study of induction chemotherapy followed by gefitinib and thoracic radiotherapy (TRT) for unresectable locally advanced adenocarcinoma of the lung.Patients and methodsPatients received induction chemotherapy with cisplatin (80 mg/m², days 1 and 22) and vinorelbine (25 mg/m², days 1, 8, 22, and 29) followed by gefitinib (250 mg daily, beginning on day 43, for 1 year) and TRT (60 Gy/30 fractions, days 57–98). The primary end point was feasibility, which was defined as the proportion of patients who completed 60 Gy of TRT and received >75% of the planned dose of gefitinib without developing grade 2 or worse pneumonitis.ResultsOf the 38 enrolled patients, 23 patients [60.5% ; 80% confidence interval (CI) 48.8–71.3] completed treatment without experiencing grade 2 or worse pneumonitis. During the chemoradiation phase, grade 3–4 alanine aminotransferase elevations were observed in 37.1% of the patients. The overall response rate was 73.0% . The median survival time was 28.5 months (95% CI 22.5–38.2), and the 2-year survival rate was 65.4% .ConclusionsAlthough the results did not meet our criterion for feasibility, the toxicity was acceptable. This treatment warrants further evaluation among patients with locally advanced non-small-cell lung cancer harboring epidermal growth factor receptor mutations.     

Randomised phase III trial of second-line irinotecan plus cisplatin versus irinotecan alone in patients with advanced gastric cancer refractory to S-1 monotherapy: TRICS trial

AimThe optimal second-line regimen for treating advanced gastric cancer (AGC) remains unclear. While irinotecan (CPT-11) plus cisplatin (CDDP) combination therapy and CPT-11 monotherapy have been explored in the second-line setting, the superiority of second-line platinum-based therapies for AGC patients initially treated with S-1 monotherapy has not yet been evaluated; therefore, we aimed to examine the survival benefit of CPT-11/CDDP combination over CPT-11 monotherapy.MethodsAGC patients showing progression after S-1 monotherapy for advanced cancer or recurrence within 6 months after completion of S-1 adjuvant therapy were randomly allocated to CPT-11/CDDP (CPT-11, 60 mg/m²; CDDP, 30 mg/m², q2w) or CPT-11 (150 mg/m², q2w).ResultsSixty-eight advanced and 95 recurrent cases were evaluated. The median overall survivals were 13.9 (95% confidence interval [CI]: 10.8–17.6) and 12.7 (95% CI: 10.3–17.2) months for CPT-11/CDDP and CPT-11, respectively (hazard ratio: 0.834; 95% CI: 0.596–1.167, P = 0.288). No significant differences were observed in the secondary end-points, including progression-free survival (4.6 [95% CI: 3.4–5.9] versus 4.1 [95% CI: 3.3–4.9] months) and response rate (16.9% [95% CI: 8.8–28.3] versus 15.4% [95% CI: 7.6–26.5]). The incidences of grade 3–4 anaemia (16% versus 4%) and elevated serum lactate dehydrogenase levels (5% versus 0%) were higher for CPT-11/CDDP than for CPT-11. Exploratory subgroup analysis revealed that CPT-11/CDDP was significantly more effective for intestinal-type AGC, compared with CPT-11 (overall survival: 15.8 versus 14.0 months; P = 0.019).ConclusionNo survival benefit was observed upon adding CDDP to CPT-11 after S-1 monotherapy failure.     

A multi-institutional phase II trial of consolidation S-1 after concurrent chemoradiotherapy with cisplatin and vinorelbine for locally advanced non-small cell lung cancer

AimTo evaluate the efficacy and feasibility of the consolidation therapy of the oral fluoropyrimidine agent S-1 after concurrent chemoradiotherapy for unresectable stage III non-small cell lung cancer (NSCLC).MethodsEligible patients had unresectable stage III NSCLC with performance status of 0 or 1. Chemoradiotherapy at a total dose of 60 Gy consisted of cisplatin (80 mg/m²) on days 1 and 29, vinorelbine (20 mg/m²) on days 1, 8, 29 and 36. Sequential consolidation S-1 therapy was commenced at a dose of 80–120 mg twice daily on day 57 with two cycles of 4 weeks administration and 2 weeks withdrawal.ResultsOf the 66 patients, 65 were evaluated. Chemoradiotherapy was completed in 57 (87.7%) patients, and S-1 consolidation therapy was administered in 45 (69.2%) and completed in 31 (47.6%). Grade 3 pneumonitis developed in three patients with one dying of it. The response rate was 61.5% (95% confidence interval [CI], 48.6–73.3%). The median progression-free survival was 10.2 (95% CI, 8.6–13.7) months and median survival time 21.8 (95% CI, 15.6–27.6) months. The 1- and 3-year survival rates were 73.9% and 34.0%, respectively.ConclusionsChemoradiotherapy with cisplatin and vinorelbine followed by S-1 consolidation demonstrated a reasonable overall survival in patients with stage III NSCLC. However, less than half of the patients completed this regimen, and the additional effect of S-1 was marginal compared with historical control.We concluded that chemoradiotherapy alone is still the recommended standard treatment for patients.     

Alcohol drinking and risk of renal cell carcinoma: results of a meta-analysis

BackgroundThe role of alcohol consumption in relation with renal cell carcinoma is still unclear; a few studies have reported a beneficial effect of moderate levels of alcohol consumption, whereas it remains still under debate whether there is a dose–response association.Materials and methodsTwenty observational studies (4 cohort, 1 pooled and 15 case–control) reporting results on at least three levels of alcohol consumption were selected through a combined search with PubMed and EMBASE of articles published before November 2010. Overall relative risks (RRs) and 95% confidence intervals (CIs) were estimated using random-effects models, and both second-order fractional polynomials and random effect meta-regression models were implemented for the study of dose–risk relation.ResultsThe estimated RRs were 0.85 (95% CI: 0.80–0.92) for any alcohol drinking, 0.90 (95% CI: 0.83–0.97) for light drinking (0.01–12.49 g/day), 0.79 (95% CI: 0.71–0.88) for moderate drinking (12.5–49.9 g/day) and 0.89 (95% CI: 0.58–1.39) for heavy drinking (≥50 g/day), respectively.ConclusionOur meta-analysis supports the hypothesis of a negative effect of moderate alcohol consumption on the risk of renal cell cancer.     

The efficacy of zoledronic acid in breast cancer adjuvant therapy: a meta-analysis of randomised controlled trials

BackgroundThe effect of zoledronic acid in breast cancer adjuvant therapy concerning improvement of patient survival has yet to be confirmed. We performed a meta-analysis of published and unpublished randomised controlled trials with the aim of accurate evaluation between clinical outcome and the association of the addition of zoledronic acid to adjuvant therapy.MethodsWe searched PubMed (from 1966 to present) and online abstracts from the proceeding Annual Meetings of the American Society of Clinical Oncology (ASCO) (years 1992–2010) and online abstracts from San Antonio Breast Cancer Symposium (years 2004–2010). A total of five eligible studies including 3676 subjects and 3678 controls met our search criteria and were evaluated. Random and fixed-effects meta-analytical models were used where indicated, and between-study heterogeneity was assessed. The primary study end-points were the disease free survival (DFS). Secondary end-points were overall survival (OS), distant or loco-regional recurrence free survival and bone metastasis free survival.FindingsCompared with the control arm, adjuvant breast cancer treatment with zoledronic acid did not significantly improve overall survival, disease free survival, bone metastasis free survival, distant and locoregional recurrence free survival. However, in the postmenopausal subgroup, the addition of zoledronic acid to standard therapy could significantly improve DFS (relative risk (RR) = 0.763, 95% confidence interval (CI) 0.658–0.884, p < 0.001) and reduce the risk of distant (RR = 0.744, 95% CI 0.611–0.906, p = 0.003) and locoregional recurrence (RR = 0.508, 95% CI 0.340–0.760, p = 0.001).InterpretationAdjuvant zoledronic acid did not significantly improve the prognosis of breast cancer patients. Due to the highly variable definitions of menopause utilised in different studies, we hypothesise that zoledronic acid may have a potential effect on postmenopausal patients. Additional studies are needed to evaluate the value of adjuvant treatment of zoledronic acid in premenopausal counterparts, differing disease stages and various pathological types of breast cancer.     

Trends of cutaneous squamous cell carcinoma in the Netherlands: increased incidence rates, but stable relative survival and mortality 1989-2008

BackgroundIncidence rates of cutaneous squamous cell carcinoma (SCC) are increasing in many countries, though detailed information is scarce.ObjectivesTo describe detailed trends in incidence rates, relative survival and estimate mortality rates of SCC in the Netherlands.MethodsInformation on newly diagnosed SCC patients between 1989 and 2008 was obtained from the Netherlands Cancer Registry (NCR). Information of non-melanoma skin cancer (NMSC) mortality was obtained from Statistics Netherlands. European Standardised Rates (ESR) and Estimated Annual Percentage Change (EAPC) were calculated. Incidence rates were fitted to two different models and predicted by the best fitted model. Cohort-based and multivariate survival analyses were performed to assess changes over time.ResultsThe ESR increased from 22.2 to 35.4 per 100,000 inhabitants for males and from 7.8 to 20.5 for females. The EAPC was 6.9% (95% confidence interval: 5.8–8.7) for males and 9.2% (95% CI: 7.5–11.0) for females. Incidence rates increased for all body sites, except for the lips, where a decreasing trend for males was observed. The predicted ESR in 2020 is 46.9 per 100,000 inhabitants for males and 28.7 for females. The 5-year relative survival rate was 92.0% (95% CI: 91.3–92.8) for males and 94.9% (95% CI: 94.0–95.7) for females and remained stable over time. Overall relative survival was better for females, but females with advanced disease had a 30.4 relative excess risk of dying compared to those in stage I. This difference was 9.9 for men. The estimated mortality rate decreased with –1.9% (95% CI: –3.1% to –0.7%) annually.ConclusionsIncidence rates of SCC increased rapidly. Relative survival was high, as most SCCs were diagnosed in stage I. Nevertheless, the number of newly diagnosed patients may exceed 11,000 by 2020, emphasising the need to improve methods to prevent skin cancer.     

MC1R, SLC45A2 and TYR genetic variants involved in melanoma susceptibility in Southern European populations: Results from a Meta-analysis

Background and methodsSeven genetic biomarkers previously associated with melanoma were analysed in a meta-analysis conducted in three South European populations: five red hair colour (RHC) MC1R alleles, one SLC45A2 variant (p.Phe374Leu) and one thermosensitive TYR variant (p.Arg402Gln). The study included 1639 melanoma patients and 1342 control subjects.ResultsThe estimated odds ratio (OR) associated with carrying at least one MC1R RHC variant was 2.18 (95% confidence interval (CI): 1.86–2.55; p-value = 1.02 × 10⁻²¹), with an additive effect for carrying two RHC variants (OR: 5.02, 95% CI: 2.88–8.94, p-value = 3.91 × 10⁻⁸). The SLC45A2 variant, p.Phe374Leu, was significantly and strongly protective for melanoma in the three South European populations studied, with an overall OR value of 0.41 (95% CI: 0.33–0.50; p-value = 3.50 × 10⁻¹⁷). The association with melanoma of the TYR variant p.Arg402Gln was also statistically significant (OR: 1.50; 95% CI: 1.11–2.04; p-value = 0.0089). Adjustment for all clinical potential confounders showed that melanoma risks attributable to MC1R and SLC45A2 variants strongly persisted (OR: 2.01 95% CI: 1.49–2.72 and OR: 0.50, 95% CI: 0.31–0.80, respectively), while the association of TYR p.Arg402Gln was no longer significant. In addition, stratification of clinical melanoma risk factors showed that the risk of melanoma was strong in those individuals who did not have clinical risk factors.ConclusionIn conclusion, our results show without ambiguity that in South European populations, MC1R RHC and SCL45A2 p.Phe374Leu variants are strong melanoma risk predictors, notably in those individuals who would not be identified as high risk based on their phenotypes or exposures alone. The use of these biomarkers in clinical practice could be promising and warrants further discussion.     

Outcome, quality of life and cognitive function of patients with brain metastases from non-small cell lung cancer treated with whole brain radiotherapy combined with gefitinib or temozolomide. A randomised phase II trial of the Swiss Group for Clinical Cancer Research (SAKK 70/03)

PurposePatients with brain metastases (BM) rarely survive longer than 6 months and are commonly excluded from clinical trials. We explored two combined modality regimens with novel agents with single agent activity and radiosensitizing properties.Patients and methodsIn this randomised phase II trial patients with BM from NSCLC were randomly assigned to 30 Gy WBRT with either concomitant gefitinib (GFT) 250 mg/day continuously or temozolomide (TMZ) 75 mg/m² for 21/28 days. The primary end-point was overall survival, with quality of life and cognitive function as secondary end-points.ResultsWe enrolled 59 patients (GFT 16, TMZ 43), and 56 patients have died, mainly (80%) from disease progression. Four patients succumbed complications of the disease or corticosteroids (intestinal perforation (2), CNS haemorrhage and pulmonary emboli). Median overall survival in the gefitinib arm was 6.3 months (95% CI 2.1–14.6), and 4.9 months (95% CI 2.3–5.6) in TMZ treated patients. Fatigue was the main complaint.ConclusionsNo relevant toxicity with those therapeutic regimens was observed. Fatal outcome in three patients may have been related to corticosteroids. Cognitive function improved during treatment. However, median overall survival for all patients was only 4.9 months (95% CI 2.3–5.7) and 1-year survival 25.4% (95% CI 15.4–37.0%).     

Treatment outcome after low intensity chemotherapy [CVP] in children and adolescents with early stage nodular lymphocyte predominant Hodgkin's lymphoma - an Anglo-French collaborative report

PurposeTo examine whether three cycles of a low-intensity chemotherapy consisting of cyclophosphamide [500 mg/m² – day 1], vinblastine [6 mg/m² – days 1 and 8] and prednisolone [40 mg/m² – days 1–7] (CVP) is safe and therapeutically effective in children and adolescents with early stage nodular lymphocyte predominant Hodgkin lymphoma [nLPHL].Patients and methodsFifty-five children and adolescents with early stage nLPHL [median age 13 years, range 4–17 years] diagnosed between June 2005 and October 2010 in the UK and France are the subjects of this report. Staging investigations included conventional cross sectional as well as 18 fluro-deoxyglucose [FDG] PET imaging. Histology was confirmed as nLPHL by an expert pathology panel.ResultsOf the 45 patients, who received CVP as first line treatment, 36 [80%, 95% Confidence Interval [CI]: (68; 92)] either achieved a complete remission [CR] or CR unconfirmed [CRu], the remaining nine patients achieved a partial response. All nine subsequently achieved CR with salvage chemotherapy [n = 7] or radiotherapy [n = 2]. Ten patients received CVP at relapse after primary treatment that consisted of surgery alone and all achieved CR. To date, only three patients have relapsed after CVP chemotherapy and all had received CVP as first line treatment at initial diagnosis. The 40-month freedom from treatment failure and overall survival for the entire cohort were 75.4% (SE ± 6%) and 100%, respectively. No significant early toxicity was observed.ConclusionsOur results show that CVP is an effective chemotherapy regimen in children and adolescents with early stage nLPHL that is well tolerated with minimal acute toxicity.     

Neoadjuvant therapy for breast cancer has no benefits on overall survival or on the mastectomy rate in routine clinical practice. A population-based study with a median follow-up of 11years using propensity score matching

BackgroundEven though neoadjuvant chemotherapy has shown no benefits on overall survival (OS), it is being widely used in the treatment of breast cancer. This is based on the assumption that it may diminish the mastectomy rate and therefore be clinically relevant for patients. Our objective was to assess the impact of neoadjuvant chemotherapy on OS and on the rate of mastectomy in patients with non-metastatic primary operable breast carcinoma in routine practice.MethodsThe Cote d’Or district breast cancer registry was used to analyse the OS and mastectomy rate in patients with invasive primary operable unilateral breast cancer diagnosed between 1982 and 2006. We performed Cox proportional hazard ratio (HR) analyses for OS and multivariate logistic regression for the mastectomy rate for the overall population. Different matching methods based on the propensity score were used as sensitivity analyses to ensure that corrections for selection bias were adequate.ResultsWe analysed 1578 patients, among whom 174 had received neoadjuvant chemotherapy. Median follow-up was 11.1 years. There was no difference between the two treatment groups for OS (HR = 1.08 (95% confidence interval (CI): 0.77–1.51 for neoadjuvant chemotherapy)). The mastectomy rate was higher among patients treated with neoadjuvant chemotherapy (odds ratio 1.54 (95% CI: 1.03–2.31)). Sensitivity analyses confirmed these results: for OS, there was no difference between the two populations precisely matched using propensity scores (HR 1.08; 95% CI: 0.671–1.65).ConclusionDespite long term follow-up, neoadjuvant chemotherapy provided no benefit for either OS or the mastectomy rate in our population.     

Randomized trial on adjuvant treatment with FOLFIRI followed by docetaxel and cisplatin versus 5-fluorouracil and folinic acid for radically resected gastric cancer

BackgroundSome trial have demonstrated a benefit of adjuvant fluoropirimidine with or without platinum compounds compared with surgery alone. ITACA-S study was designed to evaluate whether a sequential treatment of FOLFIRI [irinotecan plus 5-fluorouracil/folinic acid (5-FU/LV)] followed by docetaxel plus cisplatin improves disease-free survival in comparison with 5-FU/LV in patients with radically resected gastric cancer.Patients and methodsPatients with resectable adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to either FOLFIRI (irinotecan 180 mg/m² day 1, LV 100 mg/m² as 2 h infusion and 5-FU 400 mg/m² as bolus, days 1 and 2 followed by 600 mg/m²/day as 22 h continuous infusion, q14 for four cycles) followed by docetaxel 75 mg/m² day 1, cisplatin 75 mg/m² day 1, q21 for three cycles (sequential arm) or De Gramont regimen (5-FU/LV arm).ResultsFrom February 2005 to August 2009, 1106 patients were enrolled, and 1100 included in the analysis: 562 in the sequential arm and 538 in the 5-FU/LV arm. With a median follow-up of 57.4 months, 581 patients recurred or died (297 sequential arm and 284 5-FU/LV arm), and 483 died (243 and 240, respectively). No statistically significant difference was detected for both disease-free [hazard ratio (HR) 1.00; 95% confidence interval (CI): 0.85–1.17; P = 0.974] and overall survival (OS) (HR 0.98; 95% CI: 0.82–1.18; P = 0.865). Five-year disease-free and OS rates were 44.6% and 44.6%, 51.0% and 50.6% in the sequential and 5-FU/LV arm, respectively.ConclusionsA more intensive regimen failed to show any benefit in disease-free and OS versus monotherapy.Clinical trial registrationClinicalTrials.gov Identifier: NCT01640782.     

Everolimus in metastatic renal cell carcinoma: Subgroup analysis of patients with 1 or 2 previous vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapies enrolled in the phase III RECORD-1 study

IntroductionIn the phase III RECORD-1 trial (ClinicalTrials.gov: NCT00410124), patients with metastatic renal cell carcinoma (mRCC) who progressed on previous vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFr-TKI) therapy were randomised 2:1 to everolimus 10 mg once daily (n = 277) or placebo (n = 139). Median progression-free survival (PFS) was 4.9 months with everolimus and 1.9 months with placebo (hazard ratio [HR], 0.33; P < .001). This preplanned, prospective sub-analysis evaluated PFS benefit of everolimus versus placebo in patients who had previously received 1 or 2 VEGFr-TKIs.Patients and methodsMedian PFS was estimated using the Kaplan–Meier method, and Cox proportional hazards model was used to analyse differences in PFS.ResultsAll patients (100%) received ⩾1 previous VEGFr-TKI; 26% of patients received 2 previous VEGFr-TKIs. Among patients who received 1 previous VEGFr-TKI, median PFS was 5.4 months with everolimus and 1.9 months with placebo (HR, 0.32; 95% confidence interval [CI], 0.24–0.43; P < .001). Among patients who received 2 previous VEGFr-TKIs, median PFS was 4.0 months with everolimus and 1.8 months with placebo (HR, 0.32; 95% CI, 0.19–0.54; P < .001). The everolimus safety profile was similar for both groups.ConclusionsEverolimus was associated with prolonged PFS relative to placebo in patients who received 1 or 2 previous VEGFr-TKIs. Patients who received only 1 previous VEGFr-TKI had apparently longer PFS with everolimus in reference to those who received 2 previous VEGFr-TKIs. These results support the use of everolimus as the standard of care in patients who fail initial VEGFr-TKI therapy.     

Global Lung Oncology Branch trial 3 (GLOB3): final results of a randomised multinational phase III study alternating oral and i.v. vinorelbine plus cisplatin versus docetaxel plus cisplatin as first-line treatment of advanced non-small-cell lung cancer

Background: The study compared the efficacy of a first-line treatment with day 1 i.v. vinorelbine (NVBiv) and day 8 oral vinorelbine (NVBo) versus docetaxel (DCT) in a cisplatin-based combination in advanced non-small-cell lung cancer, in terms of time to treatment failure (TTF), overall response, progression-free survival (PFS), overall survival (OS), tolerance and quality of life (QoL).Methods: Patients were randomly assigned to receive cisplatin 80 mg/m² with NVBiv 30 mg/m² on day 1 and NVBo 80 mg/m² on day 8 every 3 weeks, after a first cycle of NVBiv 25 mg/m² on day 1 and NVBo 60 mg/m² on day 8 (arm A) or cisplatin 75 mg/m² and DCT 75 mg/m² on day 1 every 3 weeks (arm B), for a maximum of six cycles in both arms.Results: From 2 February 2004 to 1 January 2006, 390 patients were entered in a randomised study and 381 were treated. The patient characteristics are as follows (arms A/B): metastatic (%) 80.5/84.8; patients with three or more organs involved (%) 45.3/40.8; median age 59.4/62.1 years; male 139/146; squamous (%) 34.2/33.5; adenocarcinoma (%) 41.6/39.3; median TTF (arms A/B in months) [95% confidence interval (CI)]: 3.2 (3.0–4.2), 4.1 (3.4–4.5) (P = 0.19); overall response (arms A/B) (95% CI): 27.4% (21.2% to 34.2%), 27.2% (21.0% to 34.2%); median PFS (arms A/B in months) (95% CI): 4.9 (4.4–5.9), 5.1 (4.3–6.1) (P = 0.99) and median OS (arms A/B in months) (95% CI): 9.9 (8.4–11.6), 9.8 (8.8–11.5) (P = 0.58). The median survival for squamous histology was 8.87/9.82 months and for adenocarcinoma 11.73/11.60 months for arms A and B, respectively. Main haematological toxicity was grade 3–4 neutropenia: 24.4% (arm A) and 28.8% (arm B). QoL as measured by the Lung Cancer Symptom Scale was similar in both arms.Conclusions: Both arms provided similar efficacy in terms of response, time-related parameters and QoL, with an acceptable tolerance profile. In the current Global Lung Oncology Branch trial 3, NVBo was shown to be effective as a substitute for the i.v. formulation. This can relieve the burden of the i.v. injection on day 8 and can optimise the hospital's resources and improve patient convenience.     

A randomized phase III adjuvant study in high-risk cervical cancer: simultaneous radiochemotherapy with cisplatin (S-RC) versus systemic paclitaxel and carboplatin followed by percutaneous radiation (PC-R): a NOGGO-AGO Intergroup Study

BackgroundSimultaneous adjuvant platinum-based radiochemotherapy in high-risk cervical cancer (CC) is an established treatment strategy. Sequential paclitaxel (Taxol) and platinum followed by radiotherapy may offer further advantages regarding toxicity.Patients and methodsAn open-labeled randomized phase III trial was conducted to compare paclitaxel (175 mg/m²) plus carboplatin (AUC5) followed by radiation (50.4 Gy) (experimental arm-A) versus simultaneous radiochemotherapy with cisplatin (40 mg/m²/week) (arm-B) in patients with stage IB–IIB CC after surgery. Primary objective was progression-free survival (PFS).ResultsOverall, 271 patients were randomized and 263 were eligible for evaluation; 132 in arm-A and 131 in arm-B appropriately balanced. The estimated 2-year PFS was 81.8% [95% confidence interval (CI) 74.4–89.1] in arm-B versus 87.2% (95% CI 81.2–93.3) in arm-A (P = 0.235) and the corresponding 5-year survival rates were 85.8% in arm-A and 78.9% in arm-B (P = 0.25). Hematological grade 3/4 toxicity was higher in arm-B. Alopecia (87.9% versus 4.1%; P < 0.001) and neurotoxicity (65.9% versus 15.6%; P < 0.001) were significantly higher in arm-A. Early treatment termination was significantly more frequent in arm-B than in arm-A (32.1% versus 12.9%; P = 0.001).ConclusionsSequential chemotherapy and radiation in high-risk CC could not show any significant survival benefit; however, a different toxicity profile appeared. This sequential regime may constitute an alternative option when contraindications for immediate postoperative radiation are present.     

Platinum-based chemotherapy in metastatic breast cancer: the Leicester (U.K.) experience

AimsAfter failure of anthracycline- and taxane-based chemotherapy in metastatic breast cancer, treatment options until recently were limited. Until the introduction of capecitabine and vinorelbine, no standard regimen was available. We conducted a retrospective study to determine the efficacy and toxicity of platinum-based chemotherapy in metastatic breast cancer.Materials and methodsForty-two women with metastatic breast cancer previously treated with anthracyclines (93%) and/or taxanes (36%) received mitomycin–vinblastine–cisplatin (MVP) (n = 23), or cisplatin–etoposide (PE) (n = 19), as first-, second- and third-line treatment at a tertiary referral centre between 1997 and 2002. Chemotherapy was given every 3 weeks as follows: mitomycin-C (8 mg/m²) (cycles 1, 2, 4, 6), vinblastine (6 mg/m²), and cisplatin (50 mg/m²) all on day 1; and cisplatin (75 mg/m²) and etoposide (100 mg/m²) on day 1 and (100 mg/m²) orally twice a day on days 2–3.ResultsThe response rate for 40 evaluable patients (MVP: n = 23; PE: n = 17) was 18% (95% confidence interval [CI]: 9–32%). The response rate to MVP was 13% (95% CI: 5–32%, one complete and two partial responses) and to PE 24% (10–47%, four partial responses). Disease stabilised in 43% (26–63%) and 47% (26–69%) of women treated with MVP and PE, respectively. After a median follow-up of 18 months, 37 women (MVP: n = 19; PE: n = 18) died from their disease. Median (range) progression-free survival and overall survival were 6 months (0.4–18.7) and 9.9 months (1.3–40.8), respectively. Median progression-free survival for the MVP and PE groups was 5.5 and 6.2 months (Log-rank, P = 0.82), and median overall survival was 10.2 and 9.4 months (Log-rank, P = 0.46), respectively. The main toxicity was myelosuppression. Grades 3–4 neutropenia was more common in women treated with PE than in women treated with MVP (74% vs 30%; P = 0.012), but the incidence of neutropenic sepsis, relative to the number of chemotherapy cycles, was low (7% overall). The toxicity-related hospitalisation rate was 1.2 admissions per six cycles of chemotherapy. No treatment-related deaths occurred. MVP and PE chemotherapy have modest activity and are safe in women with metastatic breast cancer.