Pegylated liposomal doxorubicin in combination with gemcitabine: a phase II study in anthracycline-naïve and anthracycline pretreated metastatic breast cancer patients

Background: The aim of the study was to assess the toxicity profile, activity in terms of response rate, time to progression, overall survival, and quality of life of pegylated liposomal doxorubicin (PLD) and gemcitabine combination in chemo-naïve and pretreated metastatic breast cancer (MBC) women. Methods: Patients were eligible if they had disease progression to prior chemotherapy (anthracycline-including or not) for early breast cancer or MBC. Patients received PLD 25 mg/m² intravenously on day 1 plus gemcitabine 800 mg/m² intravenously on days 1 and 8 of each 21-day cycle. Results: Of 50 patients enrolled, 37 had received prior adjuvant chemotherapy (24 with an anthracycline) and 23 prior chemotherapy for metastatic disease (6 with an anthracycline). Two complete responses and 20 partial responses were achieved in 46 assessable patients (overall response rate: 47.8%). Responses were observed in 14 (46.6%) of 30 patients with previous anthracycline exposure. Median response duration was 7 months, median duration of clinical benefit 8 months, time to progression 7 months. At a median follow-up of 10 months, 79.4% patients were alive at 1 year. No neutropenic complication was observed. Non-hematological toxicities were mild. One patient previously treated with an anthracycline developed a transient decrease (26%) in the left ventricular ejection fraction, with cardiac function recovering within 6 months. Conclusion: Because of the non-overlapping toxicity profiles of both PLD and gemcitabine, this combination can be regarded as a reliable therapeutic option for patients who have failed previous treatments, including anthracycline, for MBC.     

Dose-escalation phase I study in metastatic breast cancer patients with combination of paclitaxel and tegafur·uracil

The study present the results of the dose-setting study of concomitant weekly administration of paclitaxel and tegafur·uracil (UFT) for metastatic breast cancer. Eligible patients who entered the study underwent two or more courses of weekly paclitaxel + UFT therapy as the protocol therapy. The initial dose (level 1) was paclitaxel, 80 mg/m(2) and UFT, 400 mg/day. At level 2, paclitaxel remained the same, but UFT was increased to 600 mg/day. At level 3, only paclitaxel was increased to 90 mg/m(2). Twelve patients were enrolled in this study between September 2000 and September 2002. Three patients were assigned to level 1. Grade 3 liver dysfunction (increased aspartate aminotransferase and alanine aminotransferase) was noted in one patient and grade 4 neutropenia was noted in one patient, showing that dose-limiting toxicity was detected in 2/3 patients. In accordance with the protocol, UFT was fixed at 400 mg/day and paclitaxel was decreased to 60 mg/m(2) at level -1, and then increased to 70 mg/m(2) at level 0. The overall effective rate after completion of two courses was 33% (3/9) including one case of complete response and two cases of partial responses. The remaining patients presented with stable diseases and no patient had progressive disease. In this study, weekly paclitaxel with concomitant UFT was administered. The recommended doses of paclitaxel and UFT were determined to be 70 mg/m(2) and 400 mg/day, respectively. As the toxicity profile shows, the highest toxicity level of this regimen was neutropenia and liver dysfunction, and dose-limiting toxicity was neutropenia.     

Single-agent oxaliplatin in pretreated advanced breast cancer patients: A?phase II study

Purpose:Oxaliplatin (L-OHP), a new platinum analogue, is anactive drug in colorectal and ovarian cancer. In this phase II study weexplored tolerability and activity of oxaliplatin as a single agent inmetastatic breast carcinoma patients. Patients and methods:Fourteen anthracycline pretreated advancedbreast cancer patients were enrolled. Oxaliplatin was given at 130mg/m² on day 1 and repeated every three weeks. Analysis oftoxicity, response rate and survival was performed. Results:The median number of courses per patient was four (range2–6). The median administered dose-intensity was 43.3mg/m²/week (range 32.5–43.3) which represents 100% ofprojected dose-intensity. No severe toxicity was encountered. Three patientsdeveloped acute transient laryngeal symptoms. Three patients displayed apartial response (21%), (95% confidence interval (CI):0%–43%), two stable disease (14%) and nineprogressed (64%). Response lasted five, four and five monthsrespectively. Median survival was 12 months. Conclusions:In this limited experience, oxaliplatin appeared tobe well tolerated and moderately active in advanced anthracycline-pretreatedbreast cancer patients. Combination chemotherapy with other active drugs suchas 5-fluorouracil (5-FU), anthracyclines and taxanes should represent the nextstep of development of this new drug.     

Does long-term application of granulocyte colony-stimulating factor adversely influence overall survival in patients with ovarian cancer? A clinical study

The purpose of this study was to investigate the effect of long-term administration of G-CSF with regard to its impact on overall survival of patients with ovarian cancer. We report the results of a non-randomized trial on 64 patients with advanced ovarian cancer treated with 6 cycles of conventional chemotherapy. Chemotherapy comprised carboplatin 400 mg/m2 and epirubicin 70 mg/m2 on day 1 of each cycle and prednimustine 100 mg/m2 on days 3 to 7, every 28 days. Thirty-three patients received CEP chemotherapy with G-CSF support whereas 31 women received CEP chemotherapy alone. The schedule of G-CSF was 5 mg/kg/day subcutanously on days 8 to 21 of each cycle. The severity of reduction in white cells and neutrophil count was significantly different in the two treatment groups (p<0.05), with more toxicity in the non- G-CSF group. G-CSF users had a non significant 0.88-fold lower risk of dying from ovarian cancer (95% CI, 0.48-1.60, p=0.678). In a survival analysis using a Cox proportional hazards model, residual tumor remained as an independent prognostic factor. The increasing amount of residual tumor resulted in a 1.767-fold higher risk (95% CI, 1.23-2.53, p=0.002) of death secondary to the underlying disease. In conclusion, this trial has failed to demonstrate any negative impact on patients' overall survival for the additional use of G-CSF with platinum-based chemotherapy; our results were consistent with the beneficial effects of G-CSF treatment on cytotoxic chemotherapy-induced myelosuppression.     

Α multicenter phase II study of pegylated liposomal doxorubicin in combination with irinotecan as second-line treatment of patients with refractory small-cell lung cancer

Purpose  

To evaluate efficacy and toxicity of a combination of pegylated liposomal doxorubicin and irinotecan in patients with refractory small-cell lung cancer.     

All-oral combination of lapatinib and capecitabine in patients with brain metastases from HER2-positive breast cancer – A phase II study

PurposeApproximately one-third of patients with advanced, HER2+ve breast cancer (BC) develop brain metastases (BMs). The aim of this study is to investigate efficacy and tolerability of the combination of lapatinib and capecitabine (LC) in HER2+ve BC patients with brain metastases (BCBM).Patients and methodsBetween January 2011 and January 2013, 21 patients with HER2+ve BCBM were included. Sixteen patients (76.19%) progressed after whole brain radiotherapy (WBRT) and 5 patients (23.81%) were treatment-naïve for BM. Patients received lapatinib (1250 mg/day continuously) and capecitabine (2000 mg/m² on days 1–14 of a 21-day cycle). All patients were treated with trastuzumab either in the adjuvant or metastatic setting. No patients had received prior lapatinib and/or capecitabine. End-points were response rate (RR), progression free survival (PFS), overall survival (OS) and toxicity.ResultsThe overall response rate (ORR) was 33.3% (7/21) and all were partial response. For patients receiving prior WBRT and patients receiving LC as first line treatment for BCBM the ORR was 31.2% (5/16) and 40.0% (2/5) respectively. Median PFS was 5.5 months. Median OS was 11 months. Treatment-related adverse events were manageable. Grade 3–4 toxicities were hand-foot syndrome (14.3%), diarrhea (14.3%), nausea/vomiting (9.5%), mucositis (4.8%), and skin rash (4.8%).ConclusionThe combination of LC is active and well-tolerated treatment in patients with HER2+ve BCBM.     

A phase II study of S-1 in patients with metastatic breast cancer — A Japanese trial by the S-1 cooperative study group, breast cancer working group

BACKGROUND: S-1 is a newly developed novel oral dihydrouracil dehydrogenase inhibiting fluoropyrimidine drug consisting of 1 M tegafur (FT), 0.4 M 5-chloro-2, 4-dihydroxypyrimidine (gimeracil), and 1 M potassium oxonate (oteracil), with efficient antitumor activity and low gastrointestinal toxicity which is widely used in Japan against advanced gastric, head and neck cancers. We investigated its clinical efficacy against metastatic breast cancer. METHODS: A non-blind phase II study was carried out to evaluate the efficacy and toxicity in metastatic breast cancer patients. Patients with measurable metastasis foci (n=111) were enrolled, and 108 patients were regarded as eligible. S-1 was administered orally at a standard dose of 80 mg/m2/day b.i.d. One course consisted of 28 consecutive days of administration followed by a 14-day rest, and courses were repeated up to six times. RESULTS: Among the eligible patients, 10 had a complete response and 35 had a partial response, with an overall response rate (CR+PR) of 41.7% (95% confidence interval: CI, 32.3-51.5%). The incidences of toxicity (> or =grade 3) were neutropenia 9.1%, anemia 0.9%, anorexia 3.6%, stomatitis 1.8%, nausea/vomiting 1.8%, diarrhea 0.9%, and fatigue 2.7%, however no treatment-related deaths were observed. The median survival time was 872 days (95% CI, 572-1,110 days). There was no difference in response rate or toxicity between the under 65-year-old group and the older group. CONCLUSION: S-1 was demonstrated to have high efficacy with low gastrointestinal toxicity even in older patients and will be a promising new chemotherapy drug for metastatic breast cancer.     

Long-term gemcitabine administration in heavily pretreated Japanese patients with metastatic breast cancer: additional safety analysis of a phase?II study

Background

Recently gemcitabine has been approved for treatment of metastatic or recurrent breast cancer in Japan; however, no systematically investigated safety study of long-term gemcitabine monotherapy has been reported despite its wide use globally for multiple indications.

Patients and methods

In a previously reported phase?II study, 62 Japanese metastatic breast cancer patients with progressive disease after treatment with anthracyclines and taxanes were treated with gemcitabine 1250?mg/m² on days?1 and 8 of a 21-day cycle. For this report we re-analyzed the safety profiles for the 13 patients who received 10 or more cycles of the therapy.

Results

Most grade?3/4 adverse events seen after 10 cycles were hematological toxicities. These were similar to those seen before the 10th cycle; however, 2 patients showed grade?3 nonhematological severe adverse events including acute cardiac failure and loss of consciousness. All adverse events were reversible and manageable. One patient received gemcitabine treatment for up to 54 cycles without unmanageable toxicities.

Conclusion

Toxicities seen in long-term gemcitabine treatment were reversible and manageable in this setting of heavily pretreated Japanese metastatic breast cancer patients.     

Carboplatin activity in untreated metastatic breast cancer patients — results of a phase II study

Summary Due to the favourable results previously obtained with cisplatin in breast cancer (54%_response rate), we studied a second-generation platinum analogue, carboplatin, in patients with previously untreated breast cancer. A total of 20 patients were entered in the study and all were evaluable. The median age was 57 years and all patients were in menopause. Karnofsky scores of 80–100 and 40–70 were registered in 14 and 6 cases, respectively. The predominant metastatic site was soft tissue in 12 subjects, visceral organs in 5 and bone in 3; 14 patients had >2 metastatic sites. Carboplatin was given i. v. at a dose of 400 mg/m² on day 1, with a 3-week rest period. In 13 patients who did not respond or whose disease recurred after carboplatin treatment, the CMFVP, CAP or FAC regimen was given as second line treatment. Carboplatin activity was observed in 4 patients [2 complete remissions (CRs) and 2 partial responses (PRs)], for a response rate of 20% (4/20); the 2 PRs were observed in soft tissue and bone and the 2 CRs, in lung, liver and bone. Remission lasted 2–10 months ( , 4 months). CMFVP given as second-line chemotherapy to 13 patients produced 7 PRs (7/13, 54%). Toxicity was moderate, producing no drugrelated deaths. Anemia (grade I–II) was recorded in seven patients; grade I–II leukopenia, in six; and grade III–IV leukopenia in two (median leukocyte nadir, 1,600/mm³). Thrombocytopenia was observed in three cases (grades I, II and III; median platelet nadir, 47,800/mm³). Unpleasant nausca/vomiting was pronouced (12 cases of grade III–IV) in 19 subjects. There were no cases of neuro- or nephrotoxicity. Due to permanent myelosuppression, no more than five cycles could be given. Our study showed that, unlike cisplatin, carboplatin given at a dose of 400 mg/m² has low antitumorigenic activity in breast cancer patients and produces pronounced myelotoxicity. Additional first-line chemotherapy studies using carboplatin are needed to define the antitumorigenic activity of this platinum analogueAbbreviations CMFVP cyclophosphamide, methotrexate, fluorouracil, vincrisine, prednisolone - CAP cyclophosphamide, Adriamycin, platinum - FAC fluorouracil, Adriamycin, cyclophosphamide     

Is salvage chemotherapy for metastatic breast cancer always effective and well tolerated? A phase II randomized trial of vinorelbine versus 5-fluorouracil plus leucovorin versus combination of mitoxantrone, 5-fluorouracil plus leucovorin

Metastatic breast cancer remains an incurable disease and the median overall survival has not significantly improved over the past two decades. Aims of the present randomized phase II trial were to analyse activity and toxicity of chemotherapies with single agent or with combination regimens in previously treated patients with advanced breast cancer. Ninety-nine eligible patients were randomized to receive the following chemotherapies: Arm A – 30mg/m² i.v. weekly; Arm B – leucovorin 100mg/m² i.v. followed by 5-fluorouracil 370mg/m² i.v. days 15, q 28days; Arm C – mitoxantrone 12mg/m² i.v. only day 1+leucovorin 100mg/m² i.v. followed by 5-fluorouracil 370mg/m² i.v. days 13, q 28days. Patients characteristics are comparable in the three groups. The median number of chemotherapy courses administered was 7, 6 and 5 in arm A, B and C, respectively. Objective responses were 24%, 30% and 21% and the median duration of responses were 2, 2.5 and 5.5 months in the arm A, B and C, respectively. Median overall survivals were 9.5, 9 and 9 months in the three arms. No difference was noted comparing the survivals of responding or non responding patients. General toxicity was not mild, with 27.5% of patients experiencing WHO grade 3–4 toxicities.Our results are similar in the three groups of patients and comparable to those reported by other authors. Chemotherapy applied to patients with second or subsequent recurrence allow objective responses in a small percentage of patients. Moreover responders have a negligible prolongation of survival.     

Non-pegylated liposomal doxorubicin and docetaxel in metastatic breast cancer: final results of a phase?II trial

Background  Non-pegylated liposomal doxorubicin (NPLD) has demonstrated equivalent antitumor activity to conventional doxorubicin and a significantly lower risk of cardiotoxicity when given as single agent or in combination with cyclophosphamide, but there is limited experience with the combination of NPLD and taxanes. This phase II study was performed to evaluate the efficacy and safety of the NPLD and docetaxel in patients with metastatic breast cancer. Patients and methods  A total of 51 patients were treated with NPLD (60 mg/m²) and docetaxel (75 mg/m²) in 3-weeks intervals for up to eight cycles. Results  The overall response rate was 50% and 78% of patients derived a clinical benefit. Median time to progression and overall survival were 10.0 months (95% CI, 6.9–13.1 months) and 25 months (95% CI, 22.1–29.8 months), respectively. Median duration of response was 12.0 months (95% CI 7.1–16.9). The treatment was generally well tolerated and associated with toxicities that were consistent with the known side-effects of the individual agents and of anthracycline/taxane combinations. There were no symptomatic cardiac averse events and mild asymptomatic LVEF changes were reported in five patients. Conclusions  The combination of NPLD and docetaxel is well tolerated and has high antitumour activity in MBC patients.     

Biweekly vinorelbine and tegafur/uracil in patients with metastatic breast cancer previously treated with anthracyclines and taxanes: GEICAM 2000–02 phase II study

Introduction

To assess the efficacy and safety profile of biweekly vinorelbine and tegafur/uracil (UFT) as treatment in patients with metastatic breast cancer previously treated with anthracyclines and taxanes.

Patients and methods

Patients with histologically confirmed breast cancer, measurable disease, no more than one prior chemotherapy regimen for metastatic disease, an Eastern Cooperative Oncology Group (ECOG) performance status ≤2, and adequate bone marrow, renal and liver function were eligible. Patients received vinorelbine (30 mg/m² on day 1) and UFT (250 mg/m² daily) every two weeks for 12 cycles unless progression or unacceptable toxicity was observed.

Results

Thirty-seven patients were included and received 311 cycles of chemotherapy. Efficacy and toxicity analyses were carried out on an intention-to-treat basis. The overall response rate was 35% (95% CI: 20–53). With a median follow-up of 18.6 months (95% CI: 1.0–74.3), the median time to progression was 7.0 months (96% CI: 5.2–8.9) and the median overall survival was 19.4 months (95% CI: 11.1–27.8). The most common severe toxicities were neutropenia (38% of patients) and asthenia (11% of patients).

Conclusion

The combination of biweekly vinorelbine and UFT in patients with metastatic breast cancer pretreated with anthracyclines and taxanes is a well tolerated and effective regimen. AEMPS Trial Registration No.: 00-0534.     

A phase II study of epirubicin, cisplatin and raltitrexed combination chemotherapy (ECT) in patients with advanced oesophageal and gastric?adenocarcinoma

Background:The aim of this study was to evaluate theefficacy of the combination of epirubicin, cisplatin and ralitrexed(Tomudex), ECT, in patients with advanced oesophageal or gastricadenocarcinoma. Efficacy was assessed primarily as response rate andsecondarily in terms of toxicity, time to progression and survival. Patients and methods:Twenty-one patients withhistologically and/or cytologically proven unresectable (7) ormetastatic (14) gastro-oesophageal adenocarcinoma, who hadbi-dimensionally measurable disease, with ECOG performance status 2,with adequate haematological, hepatic and renal function receivedfirst-line chemotherapy with epirubicin (50 mg/m²), cisplatin(60 mg/m²) and Tomudex (2.5 mg/m²), ECT, atthree-weekly intervals. Treatment consisted of three cycles ofchemotherapy, with a further three cycles if there was disease responseor stabilisation. Results:ECT is an active regimen inthe treatment of advanced gastro-oesophageal adenocarcinoma with anoverall intention-to-treat response rate of 29% (95%confidence intervals (CI): 11%–52%). In addition, 4(19%) patients had stable disease. Median time to progression was19 weeks (95% CI: 7–31 weeks). Median overall survival was18 weeks (95% CI: 11–24 weeks). Seventeen patients failedto complete the six cycles of treatment due to disease progression (5),toxicity (3), non-toxic death (1 pulmonary embolism, 1 cardiac), severeallergy to epirubicin (1), patient decision (1) and five patients afterthe study was discontinued early due to toxicity. There were three toxicdeaths: two due to sepsis complicating neutropaenia and one due tocardiorespiratory failure following drug induced enteritis. Ninepatients experienced grade 3 or 4 neutropaenia, two patients experiencedgrade 3 or 4 nausea and vomiting and one patient had grade 4diarrhoea. Conclusions:The combination of epirubicin,cisplatin and tomudex is active against advanced gastro-oesophagealadenocarcinoma but the toxicity suggests that further evaluation in arandomised comparison to ECF is not appropriate.     

Relapse after complete response to anthracycline‐based combination chemotherapy in metastatic breast cancer

The aim of this study was to assess the applicability of histopathological grading according to the protocol of Elston/Ellis and the Nottingham Prognostic Index (NPI) to a defined breast cancer population. The NPI is the sum of the individual scores concerning grade, tumour size, and lymph node status, each weighted according to regression coefficients of a Cox proportional hazard analysis and calculated for each individual breast cancer patient. 630 consecutive patients with invasive breast cancer diagnosed 1988–91 were retrospectively followed up and their tumours reviewed and graded. A Cox proportional hazard analysis was performed. Grade, lymph node status, and tumour size were statistically significant predictors of survival within the follow up period (median 7.2 years). Similar to NPI, a temporary index (Kalmar Prognostic Index, KPI) was derived and normalised to NPI for comparison (KPI(norm)). NPI and KPI(norm) gave similar prognostic power in spite of the differences of the patient populations from which the 2 indices were derived. Patients with NPI 4 or less had 0.66% breast cancer specific mortality during the follow up time. 14% of the patients with NPI 4.1–5 and 32% of those with an index sum 5.1–6 died from breast cancer during this time. Younger patients tended to have higher grade tumours. We advocate the common use of grade and the NPI in order to increase the comparability of groups of patients receiving different therapies.     

A phase I and pharmacologic study of capecitabine and paclitaxel in?breast?cancer patients

Background:Based on preclinical studies demonstrating that treatment with paclitaxel upregulates intratumoral thymidine phosphorylase (dTHdPase), which catalyzes the final step in the conversion of the oral fluoropyrimidine capecitabine to 5-fluorouracil (5-FU), as well as the overlapping spectra of activity for these agents, particularly in metastatic breast cancer, this phase I study evaluated the feasibility of administering capecitabine on an intermittent schedule in combination with paclitaxel in previously-treated patients with locally advanced or metastatic breast cancer. The study also sought to recommend doses for subsequent disease-specific studies, identify clinically significant pharmacokinetic interactions, and detect preliminary antitumor activity. Patients and methods:Nineteen previously treated women with metastatic breast cancer whose prior treatment included neither paclitaxel or capecitabine received one hundred one courses of capecitabine and paclitaxel. Paclitaxel was administered as a three-hour intravenous (i.v.) infusion at a fixed dose of 175 mg/m² and capecitabine was administered as 2 divided daily doses for 14 days followed by a seven-day rest period every 3 weeks. The dose of capecitabine was increased from a starting dose of 1650 mg/m²/d. The plasma sampling scheme in the first course permitted characterization of the pharmacokinetics of each agent given alone and concurrently to detect major pharmacokinetic interactions. Results:Palmar–plantar erythrodysesthesia (hand–foot syndrome) and neutropenia were the principal dose-limiting toxicities (DLT). Other toxicities included diarrhea and transient hyperbilirubinemia. Three of eight new patients treated with capecitabine 2000 mg/m²/d and paclitaxel 175 mg/m² experienced DLT in the first course, whereas none of eleven new patients treated with capecitabine 1650 mg/m²/d and paclitaxel 175 mg/m² developed DLT. Pharmacokinetic studies indicated that capecitabine did not grossly affect the pharmacokinetics of paclitaxel, and there were no major effects of paclitaxel on the pharmacokinetics of capecitabine and capecitabine metabolites. However, AUC values for the major 5-FU catabolite, fluoro-beta-alanine (FBAL), were significantly lower in the presence of paclitaxel. Two complete and seven partial responses (56% response rate) were observed in sixteen patients with measurable disease; four of six patients whose disease was previously treated with high-dose chemotherapy and hematopoietic stem-cell support had major responses. Seven of nineteen patients had stable disease as their best response. Conclusions:Recommended combination doses of capecitabine on an intermittent schedule and paclitaxel are capecitabine 1650 mg/m²/d orally for 14 days and paclitaxel 175 mg/m² i.v. every 3 weeks. The favorable preclinical interactions between capecitabine and paclitaxel, as well as the acceptable toxicity profile and antitumor activity in patients with metastatic breast cancer, support further clinical evaluations to determine an optimal role for the combination of capecitabine and paclitaxel in breast cancer and other relevant malignancies.     

A phase II study of oral eniluracil/fluorouracil in patients with anthracycline-refractory or anthracycline- and taxane-refractory advanced?breast cancer

Background:Eniluracil is an effective inactivator ofdihydropyrimidine dehydrogenase, the initial and rate limiting enzyme inthe catabolism of fluorouracil. The current study was done to determinethe objective tumour response of a 28-day oral regimen ofeniluracil–fluorouracil in patients with advanced breastcancer. Patients and methods:This was a multicentre, phase II studyin patients with anthracycline-refractory (AR) or anthracycline- andtaxane-refractory (ATR) advanced breast cancer. Oral eniluracil (10mg/m²) and fluorouracil (1 mg/m²) were taken twicedaily for 28 days of each 35-day treatment course. Results:In this study, 106 patients received treatment: 62patients in the AR stratum and 44 patients in the ATR stratum. Theobjective tumour response rate in the intent-to-treat population was18% (95% confidence intervals (CI):11%–27%), including three complete responses. Theresponse rate was similar in both strata: 19% in the AR and16% in the ATR stratum. The overall median duration of responsewas 23.6 weeks. The treatment was well tolerated with a low incidence ofgrade 3 or 4 toxicities that were considered attributable to studymedication. Conclusion:Treatment with oraleniluracil–fluorouracil was well tolerated by patients withadvanced breast cancer. The efficacy data were comparable with those ofother published studies in this group of refractory patients.     

Bevacizumab+chemotherapy versus chemotherapy alone in elderly patients with untreated metastatic colorectal cancer: a randomized phase II trial—PRODIGE 20 study results

BackgroundMetastatic colorectal cancer frequently occurs in elderly patients. Bevacizumab in combination with front line chemotherapy (CT) is a standard treatment but some concern raised about tolerance of bevacizumab for these patients. The purpose of PRODIGE 20 was to evaluate tolerance and efficacy of bevacizumab according to specific end points in this population.Patients and methodsPatients aged 75 years and over were randomly assigned to bevacizumab + CT (BEV) versus CT. LV5FU2, FOLFOX and FOLFIRI regimen were prescribed according to investigator’s choice. The composite co-primary end point, assessed 4 months after randomization, was based on efficacy (tumor control and absence of decrease of the Spitzer QoL index) and safety (absence of severe cardiovascular toxicities and unexpected hospitalization). For each arm, the treatment will be consider as inefficient if 20% or less of the patients met the efficacy criteria and not safe if 40% or less met the safety criteria.ResultsAbout 102 patients were randomized (51 BEV and 51 CT), median age was 80 years (range 75–91). Primary end point was met for efficacy in 50% and 58% and for safety in 61% and 71% of patients in BEV and CT, respectively. Median progression-free survival was 9.7 months in BEV and 7.8 months in CT. Median overall survival was 21.7 months in BEV and 19.8 months in CT. The 36-month overall survival rate was 27% in BEV and 10.1% in CT. Severe toxicities grade 3/4 were mainly non-hematologic toxicities (80.4% in BEV, 63.3% in CT).ConclusionBevacizumab combined with CT was safe and efficient. Both arms met the primary safety and efficacy criteria.     

High-dose sequential chemotherapy with recombinant granulocyte colony-stimulating factor and repeated stem-cell support for inflammatory breast cancer patients: does impact on quality of life jeopardize feasibility and acceptability of treatment?

PURPOSE: This study was designed to investigate the quality of life (QOL) of patients enrolled onto the High-Dose Chemotherapy for Breast Cancer Study Group trial (PEGASE 02), a French pilot multicenter trial of the treatment of inflammatory breast cancer (IBC) aimed at evaluating (1) toxicity and feasibility of sequential high-dose chemotherapy (HDC) with recombinant human granulocyte colony-stimulating factor (filgrastim) and stem-cell support and (2) response to HDC in terms of pathologic response and survival. PATIENTS AND METHODS: QOL measures were performed at inclusion and four times subsequently up to 1 year using an ad hoc side-effect questionnaire (19 physical symptoms) and the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30). RESULTS: Of the 95 patients entered, the overall QOL questionnaire completion compliance was 75.6%. During cycle 3 of HDC, the number of symptoms was high (mean +/- SD QOL score, 10 +/- 3), with fatigue, hair loss, appetite loss, nausea, change in taste, vomiting, fever, and weight loss reported by more than 60% of patients. Toxicity and distress associated with HDC were reflected in the decline of four EORTC QLQ-C30 scores: global QOL (P =.001), and physical, role, and social functioning (P <.001 for all statistics). However, QOL deterioration disappeared after treatment completion, except for physical functioning (P =.025). One year after inclusion, most QOL scores returned to baseline, and both emotional functioning and global QOL scores were even higher than baseline (P =.030 and P =.009, respectively). CONCLUSION: If it is confirmed that improvements in pathologic response rates with HDC effectively translate into increased probabilities of survival for IBC patients, adoption of such treatment as PEGASE 02 will not involve crucial choices between length of life and QOL and should not be delayed for QOL arguments.