Rôle de l’irradiation ganglionnaire chez les patientes indemnes d’envahissement ganglionnaire après chimiothérapie néoadjuvante pour un cancer du sein : expérience du centre René-Huguenin

PurposeNeoadjuvant chemotherapy generally induces significant changes in the pathological extent of disease. This potential down-staging challenges the standard indications of adjuvant radiation therapy. We assessed the utility of lymph node irradiation in breast cancer patients with pathological N0 status (pN0) after neoadjuvant chemotherapy and breast-conserving surgery.Patients and materialsAmong 1054 breast cancer patients treated with neoadjuvant chemotherapy in our institution between 1990 and 2004, 248 patients with clinical N0 or N1-N2 lymph node status at diagnosis had pN0 status after neoadjuvant chemotherapy and breast-conserving surgery. Cox regression analysis was used to identify factors influencing locoregional recurrence-free survival, disease-free survival and overall survival.ResultsAll 248 patients received breast irradiation, and 158 patients (63.7%) also received lymph node irradiation. With a median follow-up of 88 months, the 5-year locoregional recurrence-free survival and overall survival rates were respectively 89.4% and 88.7% with lymph node irradiation and 86.2% and 92% without lymph node irradiation (no significant difference). Survival was poorer among patients who did not have a pathological complete primary tumor response (pCR) (hazards ratio [HR] = 3.05; 95% CI, 1.17 to 7.99) and in patients with N1-N2 clinical status at diagnosis ([HR] = 2.24; 95% CI, 1.15 to 4.36). Lymph node irradiation did not significantly affect survival.ConclusionsRelative to combined breast and local lymph node irradiation, isolated breast irradiation does not appear to be associated with a higher risk of locoregional relapse or death among breast cancer patients with pN0 status after neoadjuvant chemotherapy. These results need to be confirmed in a prospective study.     

Short course of radiation therapy in elderly patients with glioblastoma multiforme

PurposeThe optimal schedule of irradiation in elderly patients suffering from glioblastoma multiforme (GBM) is unsettled.Materials and methodsThis study reviewed the charts of 28 consecutive GBM patients aged 70 years or more with a Karnofsky Performance Status (KPS) greater than or equal to 70 who received a short course of radiotherapy (40 grays in 15 fractions over three weeks).ResultsThe median age at surgery was 74.6 years (range, 70.1–85.7). No patient received prior or concomitant chemotherapy. The median progression-free survival and overall survival were 21.6 weeks (95% CI, 17.0–39.9) and 50.6 weeks (95% CI, 26.3–62.0), respectively. Even within a narrow range (< 90 or ≥ 90), KPS remained a prognostic factor (p = 0.03). Tolerance appeared acceptable in terms of KPS changes and corticosteroid use during radiation therapy.ConclusionThese results support the efficacy of short schedule radiotherapy for GBM in elderly patients with a good KPS.     

Radiothérapie stéréotaxique de carcinomes bronchiques primitifs : suivi non invasif de la cible en temps réel

PurposeStereotactic radiation therapy using the CyberKnife^® has been introduced in France in 2006. Two treatment modalities are currently available: the first one (Synchrony^®) is a real-time fiducial-based target tracking system, while the other (Xsight Lung Tracking [XLT] System^®) is completely fiducial-free.Patients and methodsSixty-eight patients were treated for a pulmonary tumor between June 2007 and November 2009. Since august 2008, the XLT System^® was used for 26 patients. We report the necessary conditions for the XLT System (position, laterality and size of the tumor), the toxicity and outcome of this treatment.ResultsTwenty-two patients were analyzed. Median follow-up was 6 months (min = 3; max = 16). Local control rate was 100%. The main toxicity was grade grade 1 pulmonary alveolitis (27%). No grade 3 or 4 toxicities were reported.ConclusionThe high local control rate and low toxicity obtained with the CyberKnife^® XLT System^® suggest that such treatment is an alternative for inoperable patients.     

Étude pilote française de phase II d’irradiation partielle accélérée du sein conformationnelle tridimensionnelle bi-fractionnée hebdomadaire de 40 Gy

PurposeSince 2009, accelerated partial breast irradiation (APBI) in North America has been allowed to be used for selected group of patients outside a clinical trial according to the ASTRO consensus statement. In France, accelerated partial breast irradiation is still considered investigational, several clinical trials have been conducted using either intraoperative (Montpellier) or Mammosite^® (Lille) or brachytherapy modality (PAC GERICO/FNCLCC). Here, we report the original dosimetric results of this technique.Patients and methodsSince October 2007, Institut Gustave-Roussy has initiated a phase II trial using 3D-conformal accelerated partial breast irradiation (40 Gy in 10 fractions BID in 1 week). Twenty-five patients with pT1N0 breast cancer were enrolled and were treated by two minitangent photons beams (6 MV) and an “en face” electron beam (6–22 MeV).ResultsThe mean clinical target volume and planning target volume were respectively 15.1 cm³ (range: 5.2–28.7 cm³) and 117 cm³ (range: 52–185 cm³). The planning target volume coverage was adequate with at least a mean of 99% of the volume encompassed by the isodose 40 Gy. The mean dose to the planning target volume was 41.8 Gy (range: 41–42.4 Gy). Dose inhomogeneity did not exceed 5%. Mean doses to the ipsilateral lung and heart were 1.6 Gy (range: 1.0–2.3 Gy) and 1.2 Gy (range: 1.0–1.6 Gy), respectively.ConclusionThe 3D conformal accelerated partial breast irradiation using two minitangent and “en face” electron beams using a total dose of 40 Gy in 10 fractions BID over 5 days achieves appropriate planning target volume coverage and offers significant normal-tissue sparing (heart, lung). Longer follow-up is needed to evaluate the tissue tolerance to this radiation dose.     

Haute dose dans la prostate par radiothérapie guidée par l’image : apport de l’arcthérapie avec modulation d’intensité du faisceau

PurposeTo compare two Intensity Modulated Radiation Therapy (IMRT) techniques for prostate cancer: the Volumetric Modulated Arc Therapy (VMAT) and the “Step and Shoot” technique (S&;S).Materials and methodsVMAT and S&;S plans (RX 18 MV) were created and compared (Wilcoxon test) for 10 patients. The dosimetric goal of both treatments was to deliver 46 Gy to the seminal vesicles and 80 Gy to the prostate, while respecting the dose constrains in the organs at risk of toxicity. For one patient, the two techniques were compared for dose painting and escalation in target volumes defined on MRI and registered thanks to intraprostatic fiducials.ResultsVMAT, compared to S&;S, offered: an increase of the PTV2s (prostate) volume receiving 77 to 80 Gy and a decrease of V₈₂ and V₈₃; a decrease of V₄ to V₆, V₁₆ to V₂₃, and V₆₉ to V₇₃ for the rectal wall; a decrease of V₂₅ for the bladder wall; a decrease of V₂₁ to V₄₃ for the femoral heads; a decrease of V₂₆ to V₄₄ and V₇₂ to V₈₀ but an increase of V₁ to V₂₁ and V₄₉ to V₆₀ for the healthy tissues. The Conformal Index “COIN” was better with VMAT than S&;S (0.60 to 0.66). The delivered MU were significantly reduced with VMAT (8% mean) as well as the delivery time (4 min to 1.5 min). VMAT allowed delivering theorically 90 Gy in the peripheral zone and 100 Gy in the tumor.ConclusionIn case of prostate irradiation, VMAT shows improvement compared with S&;S. In particular, organs at risk are better spared, the delivery time is shortened and the number of delivered UM is decreased.     

Mitomycin C with continuous fluorouracil or with cisplatin in combination with radiotherapy for locally advanced anal cancer (European Organisation for Research and Treatment of Cancer phase II study 22011-40014)

PurposeTo assess the feasibility and activity of radio-chemotherapy with mitomycin C (MMC) and cisplatin (CDDP) in locally advanced squamous cell anal carcinoma with reference to radiotherapy (RT) combined with MMC and fluorouracil (5-FU).Patients and methodsPatients with measurable disease >4 cm N0 or N+ received RT (36 Gy + 2 week gap + 23.4 Gy) with either MMC/CDDP or MMC/5-FU (MMC 10 mg/m² d1 of each sequence; 5-FU 200 mg/m²/day c.i.v. daily; CDDP 25 mg/m² weekly). Forty patients/arm were needed to exclude a RECIST objective response rate (ORR), 8 weeks after treatment, of <75% (Fleming 1, α = 10%, β = 10%).ResultsThe ORR was 79.5% (31/39) (lower bound confidence interval [CI]: 68.8%) with MMC/5-FU versus 91.9% (34/ 37) (lower bound CI: 82.8%) with MMC/CDDP. In the MMC/5-FU group, two patients (5.1%) discontinued treatment due to toxicity versus 11 (29.7%) in the MMC/CDDP group. Nine grade 3 haematological events occurred with MMC/CDDP versus none with 5-FU/MMC. The rate of other toxicities did not differ. There was no toxic death. Thirty-one patients in the MMC/5-FU arm (79.5%) and 18 in the MMC/CDDP arm (48.6%) were fully compliant with the protocol treatment (p = 0.005).ConclusionsRadio-chemotherapy with MMC/CDDP seems promising as only MMC/CDDP demonstrated enough activity (RECIST ORR >75%) to be tested further in phase III trials; MMC/5-FU did not. MMC/CDDP also had an overall acceptable toxicity profile.     

Magnesium depletion in patients receiving cisplatin-based chemotherapy

AimsTo assess the incidence of hypomagnesaemia, the influence of different cisplatin dosages on the degree of hypomagnesaemia and the effect of routine magnesium supplementation on magnesium levels.Materials and methodsMagnesium levels for 214 consecutive patients receiving cisplatin-based chemotherapy were studied. Twenty different chemotherapy regimens were prescribed. Doses ranged from 7 to 51 mg/m²/week. The interval between cycles ranged from 1 to 4 weeks. The number of evaluable cycles ranged from one to eight. Patients receiving bleomycin, etoposide and cisplatin (BEP) chemotherapy routinely received 60 mmol magnesium per cycle; patients receiving cisplatin, vincristine, methotrexate, bleomycin — dactinomycin, cyclophosphamide, etoposide (POMB–ACE) chemotherapy routinely received 20 mmol magnesium per cycle. For all other chemotherapy regimens, magnesium was not routinely prescribed.ResultsBaseline magnesium levels were available for 195 patients, 92% were within the normal range. The average level was 0.82 mmol/l. There was a statistically significant decrease in magnesium levels from baseline to the lowest magnesium level (mean = 0.68 mmol/l, standard deviation = 0.13) (P < 0.0005). The incidence of hypomagnesaemia (serum magnesium < 0.7 mmol/l) at any point during chemotherapy was 43%. Multiple regression analysis showed a significant association between dose, frequency, and number of cycles given, and the degree of hypomagnesaemia (P = 0.001, P = 0.03 and P < 0.0005, respectively). Routine magnesium supplementation significantly reduced the degree of hypomagnesaemia if sufficient amounts of magnesium are given: 60 mmol magnesium per cycle for a regimen containing 33 mg/m²/week cisplatin is sufficient; 20 mmol magnesium per cycle for a regimen containing 40 mg/m²/week cisplatin is insufficient.ConclusionsIt is recommended that magnesium levels should be measured routinely in all patients receiving cisplatin and that all cisplatin-based chemotherapy regimens should be supplemented routinely with sufficient doses of magnesium (40–80 mmol magnesium per cycle depending on the regimen).     

Randomised phase III trial of adjuvant chemotherapy with oral uracil and tegafur plus leucovorin versus intravenous fluorouracil and levofolinate in patients with stage III colorectal cancer who have undergone Japanese D2/D3 lymph node dissection: Final results of JCOG0205

BackgroundNSABP C-06 demonstrated the non-inferiority of oral adjuvant uracil and tegafur plus leucovorin (UFT/LV) to weekly fluorouracil and folinate (5-FU/LV) with respect to disease-free survival (DFS) for stage II/III colon cancer. This is the first report of JCOG0205, which compared UFT/LV to standard 5-FU/levofolinate (l-LV) for stage III colorectal cancer patients who have undergone Japanese D2/D3 lymph node dissection.MethodsPatients were randomised to three courses of 5-FU/l-LV (5-FU 500 mg/m², l-LV 250 mg/m² on days 1, 8, 15, 22, 29, 36 every 8 weeks) or five courses of UFT/LV (UFT 300 mg m⁻² day⁻¹, LV 75 mg/day on days 1–28 every 5 weeks). The primary end-point was DFS. The sample size was 1100 determined with one-sided alpha of 0.05, power of 0.78 and non-inferiority margin of hazard ratio of 1.27. This trial is registered with UMIN-CTR (C000000193).FindingsBetween February 2003 and November 2006, 1,101 patients (1092 eligible patients) were randomised to 5-FU/l-LV (n = 550) or UFT/LV (n = 551). Median age: 61 years, colon/rectum: 67%/33%, number of positive nodes ⩽3/>3: 73%/27%, stage IIIa/IIIb: 75%/25%. The hazard ratio of DFS was 1.02 (91.3% confidence interval, 0.84–1.23), demonstrating the non-inferiority of UFT/LV (P = 0.0236). Five-year overall survival (87.5%) was higher than that in NSABP C-06 (69.6%). Grade 3/4 toxicities were 8.4% neutropenia in 5-FU/l-LV and 8.7% alanine aminotransferase elevation in UFT/LV, respectively. The incidences of diarrhoea (9.6% versus 8.5%) and anorexia (4.0% versus 3.7%) were similar between the two arms. No treatment-related deaths were reported.InterpretationAdjuvant UFT/LV is non-inferior to standard 5-FU/l-LV with respect to DFS. UFT/LV should be an oral treatment option for patients with stage III colon cancer who have undergone Japanese D2/D3 lymph node dissection.     

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.     

Preliminary results of consolidation chemotherapy following concurrent chemoradiation after radical surgery in high-risk early-stage carcinoma of the uterine cervix

AimsTo evaluate the efficacy and toxicity of consolidation chemotherapy after concurrent chemoradiation (CCRT) with 5-fluorouracil (5-FU) and cisplatin in the treatment of high-risk, early stage cervical carcinoma after radical surgery.Materials and methodsWomen with clinical stage IB and IIA cervical carcinoma, initially treated with radical hysterectomy and pelvic lymphadenectomy, and who had positive pelvic lymph nodes, positive margins, parametrial involvement, or all three, were divided into either a CCRT alone group or a consolidation chemotherapy after CCRT group. Three cycles of chemotherapy were given to the CCRT alone group, and six cycles to the consolidation chemotherapy group. Women in each group received 50.4 Gy external radiation in 28 fractions to a standard pelvic field. Chemotherapy consisted of cisplatin 60 mg/m² (× 1) and 5-FU 1000 mg/m²/d (× 5) every 3 weeks, with the first and second cycles given concurrent with radiation. Survival and toxicity were compared between the two groups.ResultsForty women were evaluable (25 in the CCRT alone group and 15 in the consolidation chemotherapy group). The estimated 2-year progression-free survival was 87.7% in the CCRT alone group and 67.0% in the consolidation chemotherapy group. The estimated 2-year overall survival was 95.8% in the CCRT alone group and 100% in the consolidation chemotherapy group. However, no significant differences were found in progression-free and overall survival in the two groups (P = 0.17 and P = 0.29, respectively). Grade 2 or higher leukopenia and neutropenia were significantly more frequent in the consolidation chemotherapy group than in the CCRT alone group (P = 0.02 and P < 0.01, respectively).ConclusionsAlthough the sample size was small, and this study was not randomised, these results suggest that consolidation chemotherapy may not improve survival. Rather, it may increase haematologic toxicities for women with high-risk, early stage cervical carcinoma who undergo radical surgery followed by CCRT.     

Cisplatin and gemcitabine administered every two weeks in patients with locally advanced or metastatic urothelial carcinoma and impaired renal function

BackgroundCisplatin-based combination chemotherapy is the mainstay of treatment for locally advanced or metastatic urothelial carcinoma. However, standard dose schedule of cisplatin cannot be used in patients with impaired renal function. We evaluated the safety and efficacy of gemcitabine and a split dose administration of cisplatin in patients with renal dysfunction.Patients and methodsPatients with locally advanced or metastatic urothelial carcinoma with creatinine clearance between 35 and 59 ml/min received gemcitabine 2500 mg/m² and cisplatin 35 mg/m² on day 1 and day 15 for an every 28 day schedule.ResultsBetween March 2004 and November 2009, 38 patients were treated. Median creatinine clearance was 49 ml/min. Median number of cycles per patient was 3 (1–7). There were 15 partial responses (39%) and 12 patients had stable disease (31%). Median progression free survival and overall survival were 3.5 and 8.5 months (mo), respectively.Grade 3–4 haematological toxicities were: neutropenia 9%, anaemia 6% and thrombocytopenia 16%. No patient developed renal toxicity.ConclusionsBiweekly gemcitabine and cisplatin is an active and feasible regimen in this subset of patients and could be an option for unfit patients. However, results seem not to be superior to those obtained with carboplatin based regimens in this population of patients.     

Comparison of induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by radiation vs concurrent chemoradiotherapy with TPF in patients with locally advanced squamous cell carcinoma of the head and neck

AimsTo compare the effectiveness of induction chemotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF) followed by radiation with that of concurrent chemoradiotherapy with TPF in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN).Materials and methodsIn a group of patients receiving induction chemotherapy followed by radiation, 15 patients received two cycles of chemotherapy with docetaxel 60 mg/m², cisplatin 70 mg/m² and 5-day 5-fluorouracil (5-FU) 750 mg/m²/day. Radiotherapy was begun 21 days after completing chemotherapy. In the group receiving concurrent chemoradiotherapy, 19 patients received two cycles of chemotherapy with docetaxel 50 mg/m², cisplatin 60 mg/m², and 5-day 5-FU 600 mg/m²/day. Radiation was begun on the first day of chemotherapy. The total radiation dose was between 63 and 74 Gy.ResultsOverall response rate (partial and complete response — both 100%) and complete response rate (87% and 84%) were similar, but, in overall survival, concurrent chemoradiotherapy with TPF was better than induction chemotherapy with TPF followed by radiation. Mucositis and anaemia were more frequent in the group receiving concurrent chemoradiotherapy, but the group receiving concurrent chemoradiotherapy with TPF improved overall survival.ConclusionsThis is a small non-randomised comparison. The effectiveness of concurrent chemoradiotherapy with TPF was better than that of induction chemotherapy with TPF followed by radiation.     

Survival without toxicity for cisplatin plus pemetrexed versus cisplatin plus gemcitabine in chemonaïve patients with advanced non-small cell lung cancer: A risk-benefit analysis of a large phase III study

BackgroundIn a large phase III study, cisplatin and pemetrexed had non-inferior efficacy and better tolerability compared with cisplatin and gemcitabine in chemonaïve patients with non-small cell lung cancer (NSCLC). The current analysis characterised the clinical benefit (i.e. survival) relative to clinical risk (i.e. drug-related toxicity) of the doublets.Patients and methodsA total of 1669 patients (of 1725 randomised) received 500 mg/m² pemetrexed IV followed by 75 mg/m² cisplatin IV on day 1 or gemcitabine 1250 mg/m² on days 1 and 8 and 75 mg/m² cisplatin on day 1, administered every 3 weeks for up to 6 cycles. Survival without toxicity (i.e. clinical benefit to risk) was defined as the time from randomisation to the first occurrence of any grade 3 or 4 drug-related toxicity or death, and was analysed using Kaplan–Meier and Cox methods.ResultsIn the overall patient population, survival without grade 3 or 4 drug-related toxicity was significantly longer for patients treated with cisplatin and pemetrexed versus cisplatin and gemcitabine (HR = 0.70; P < 0.001), as was survival without grade 4 drug-related toxicity (HR = 0.83; P < 0.001). For patients with non-squamous NSCLC, survival without toxicity with cisplatin and pemetrexed was superior to cisplatin and gemcitabine for grade 3 or 4 drug-related toxicity (HR = 0.64; P < 0.001) and for grade 4 drug-related toxicity (HR = 0.77; P < 0.001), whereas no treatment-arm difference was observed in the squamous subgroup.ConclusionsPatients with non-squamous NSCLC treated with front-line cisplatin and pemetrexed have superior survival without toxicity (i.e. clinical benefit-to-risk profile) compared with patients treated with cisplatin and gemcitabine.     

The efficacy of adjuvant chemotherapy with 5-fluorouracil in colorectal cancer depends on the mismatch repair status

AimsThe aim of this study is to evaluate if mismatch repair (MMR) defective colorectal cancer has a different response to adjuvant 5-fluorouracil (5-FU) chemotherapy in a cohort of patients prospectively followed during 5 years.MethodsThe cohort included 754 surgically treated patients with colorectal cancer. MMR status was diagnosed by MLH1 and MSH2 immunohistochemistry and microsatellite instability analysis. Median follow-up was 49.2 months (range 1–73). At inclusion, 505 patients were diagnosed as TNM II or III stage, analysis of the efficacy of adjuvant chemotherapy was made on this population. Adjuvant chemotherapy was applied to 248 patients (98.2% 5-FU based).ResultsMMR deficiency was found in 76 patients (10.1%). No differences were found in overall survival (log-rank p = 0.3) or disease-free survival (log-rank p = 0.3) regarding MMR status. Adjuvant chemotherapy improves survival in patients in the II or III stage, but this improvement is only evident in patients with MMR-competent tumours (log-rank p = 0.00001). Survival of patients with MMR-defective tumours does not improve with adjuvant chemotherapy (log-rank p = 0.7). A multivariate analysis showed an independent effect of the interaction between MMR status and adjuvant chemotherapy (Hazard ratio 2.04; 95% confidence interval: 1.42–2.93).ConclusionIn a cohort of colorectal cancer patients, those with MMR-deficient tumours seem not to benefit from 5-FU-based chemotherapy.     

Renal protection with magnesium subcarbonate and magnesium sulphate in patients with epithelial ovarian cancer after cisplatin and paclitaxel chemotherapy: a randomised phase II study

BackgroundThe aim of this study was to examine the effect of magnesium supplementation on nephrotoxicity accompanying standard cisplatin-based chemotherapy in patients with epithelial ovarian cancer (EOC).Patients and methodsA double-blind, placebo-controlled, randomised study was conducted in which study arm magnesium sulphate (5 g) was administered before each course of standard chemotherapy with paclitaxel (135 mg/m²/24 h) plus cisplatin (75 mg/m²) every 3 weeks in patients with EOC. Magnesium subcarbonate (500 mg), three times per day orally, was administered during the treatment intervals. The control arm was administered a placebo instead of both magnesium salts. Magnesium serum levels (sMg) and GFR markers: serum levels of creatinine (sCr), Cockroft–Gault (ClCG) and Modification Diet of Renal Disease (MDRD) formulae were recorded before each cycle, and 3 weeks after the sixth course.Results41 EOC patients were randomised and 40 were eligible. sMg varied significantly between the supplemented and placebo groups (p<0.0001). The control group showed a significantly greater decrease of GFR assessed by: sCr (p = 0.0069), ClCG (p = 0.0077) and MDRD (p = 0.032) formulae compared with the magnesium supplemented group.ConclusionsThese results demonstrate the nephroprotective effect of magnesium supplementation during chemotherapy with cisplatin.     

Reconstruction mammaire immédiate après mastectomie suivie de radiothérapie : facteurs de risque de complications

ObjectivesTo determine prospectively the factors associated with reconstruction failure (i.e. requiring expander removal) and capsular contracture in patients undergoing mastectomy and immediate two-stage breast reconstruction with a tissue expander and implant, and radiotherapy for breast cancer. This is a multi-institutional prospective nonrandomized trial.Patients and MethodsBetween 2/1998 and 9/2006, we prospectively evaluated 141 consecutive patients who received 141 implants after mastectomy and underwent chest wall radiotherapy (46 to 50 Gy in 23 to 25 fractions). Patients were evaluated after 24 to 36 months by two senior physicians (radiation oncologist and surgeon).ResultsMedical follow-up was 37 months. Baker 1 and 2 capsular contracture was observed in 67.5% of patients, Baker 3 and 4 in 32.5%. There were 32 reconstruction failures. In a univariate analysis, the following factors were associated with Baker 3 and 4 capsular contracture: surgeon, use of hormonotherapy and smoking, of which only one remained in the multivariate analysis: surgeon. In a univariate analysis, the following factors were associated with reconstruction failure: tumor size T3 or T4, smoking, pN+ axilla. Three factors remained associated with reconstruction failure in a multiple logistic regression: large tumors T3/T4, smoking and pN+ axilla.ConclusionsMastectomy, radiotherapy and immediate breast reconstruction with a tissue expander and implant should be considered when breast conserving surgery has been denied. Adequate patients can be easily selected by using three factors of favourable outcome.     

Weekly fluorouracil at 425 mg/m(2) plus low-dose folinic acid for 24 weeks as adjuvant treatment for colorectal cancer: assessment of toxicity and delivery

AimsTo assess the toxicity and dose delivery of weekly bolus 5-fluorouracil (5-FU) at 425 mg/m² plus low-dose folinic acid (FA) for 24 weeks as adjuvant treatment for colorectal cancer.Materials and methodsData were collected on toxicity and dose reductions, stoppages, delays and intensity from 100 consecutive patients receiving this adjuvant regimen after curative surgery.ResultsThere were 53 men and 47 women (median age: 64 and 65 years, respectively); 77 patients with colon cancer and 23 with cancer of the rectum; 34 patients with Dukes' stage B and 66 with Dukes' stage C. Thirty-seven patients experienced at least one grade 3 or 4 toxicity, mainly diarrhoea (20 patients) or fatigue (14 patients). Only one grade 4 toxicity was noted (diarrhoea). In multivariate analysis, increased grade 3 and 4 toxicity was significantly associated with female gender (P = 0.001) and age >65 years (P = 0.046). Forty patients completed the 24 cycles without dose reduction or delay. Forty-one patients required at least one dose reduction. The median ‘conventional’ dose intensity (DI), calculated from the first cycle to the last, was 408 mg/m²/week (96%). The median DI over 24 weeks was 387 mg/m²/week (91%). A higher median 24-week DI was delivered to men (407 mg/m²/week, 96%) than women (361 mg/m²/week, 85%; P = 0.009). Women older than 65 years showed a significantly reduced median DI over 24 weeks (347 mg/m²/week, 82%) compared with men aged 65 years or younger (407 mg/m²/week, 96%; P = 0.049) and men older than 65 years (425 mg/m²/week, 100%; P = 0.001), although the difference against women aged 65 years or younger (377 mg/m²/week, 89%) was not statistically significant (P = 0.09).ConclusionThis regimen has shown what might be considered high rates of grade 3 and 4 toxicity for an adjuvant treatment, although the delivered DI was acceptable. Caution is urged in the treatment of elderly female patients who have statistically higher rates of grade 3 and 4 toxicity and lower DI.     

Raltitrexed (Tomudex) versus standard leucovorin-modulated bolus 5-fluorouracil: Results from the randomised phase III Pan-European Trial in Adjuvant Colon Cancer 01 (PETACC-1)

ObjectivesPETACC-1 assessed if raltitrexed is non-inferior to 5-fluorouracil and leucovorin for relapse-free survival (RFS) and overall survival (OS) in adjuvant stage III colon cancer.MethodsNon-inferiority required both HR for RFS and OS < 1.25 at 1-sided α = 0.05. Patients (1921) were randomised to six cycles of 5-FU/LV (n = 969) or eight cycles of raltitrexed (n = 952). We report the final results in 993 eligible patients who started and completed the allocated treatment (489 5-FU/LV and n = 504 Raltitrexed) of whom respectively 146 and 148 died, respectively.ResultsThe trial closed prematurely when 17 (1.9%) raltitrexed-related deaths were reported. Haematological and gastrointestinal toxicities were more frequent with 5-FU/LV, liver toxicities with raltitrexed. Raltitrexed was stopped for toxicity in 13.2% and 5-FU/LV in 8.5%. Sixty-day mortality was 9% versus 7%. With 4.1 years median follow-up, the HR for RFS was 1.16 (90% CI 0.99–1.37) and that for OS was 1.01 (90% CI 0.84–1.23).ConclusionThe trial failed to demonstrate non-inferiority of raltitrexed.FundingFree drugs and financial support from AstraZeneca.     

Combination of cisplatin/S-1 in the treatment of patients with advanced gastric or gastroesophageal adenocarcinoma: Results of noninferiority and safety analyses compared with cisplatin/5-fluorouracil in the First-Line Advanced Gastric Cancer Study

BackgroundThe aim of developing oral fluorouracil (5-FU) is to provide a more convenient administration route with similar efficacy and the best achievable tolerance. S-1, a novel oral fluoropyrimidine, was specifically designed to overcome the limitations of intravenous fluoropyrimidine therapies.Patients and methodsA multicentre, randomised phase 3 trial was undertaken to compare S-1/cisplatin (CS) with infusional 5-FU/cisplatin (CF) in 1053 patients with untreated, advanced gastric/gastroesophageal adenocarcinoma. This report discusses a post-hoc noninferiority overall survival (OS) and safety analyses.ResultsResults (1029 treated; CS = 521/CF = 508) revealed OS in CS (8.6 months) was statistically noninferior to CF (7.9 months) [hazard ratio (HR) = 0.92 (two-sided 95% confidence interval (CI), 0.80–1.05)] for any margin equal to or greater than 1.05. Statistically significant safety advantages for the CS arm were observed [G3/4 neutropenia (CS, 18.6%; CF, 40.0%), febrile neutropenia (CS, 1.7%; CF, 6.9%), G3/4 stomatitis (CS, 1.3%; CF, 13.6%), diarrhoea (all grades: CS, 29.2%; CF, 38.4%) and renal adverse events (all grades: CS, 18.8%; CF, 33.5%)]. Hand–foot syndrome, infrequently reported, was mainly grade 1/2 in both arms. Treatment-related deaths were significantly lower in the CS arm than the CF arm (2.5% and 4.9%, respectively; P < 0.047).ConclusionCS is noninferior to CF with a better safety profile and provides a new treatment option for patients with advanced gastric carcinoma.     

Adaptive radiotherapy using helical tomotherapy for head and neck cancer in definitive and postoperative settings: initial results

AimsTo assess whether routine mid-treatment replanning in head and neck squamous cell carcinoma patients results in meaningful improvements in target or normal tissue dosimetry and to assess which patients derive the greatest benefit.Materials and methodsTwenty patients treated with either postoperative chemoradiotherapy or definitive chemoradiotherapy with primary or nodal disease ≥3 cm in size were included in this prospective pilot study. Seven patients received adjuvant chemoradiotherapy and 13 received definitive chemoradiotherapy. Patients were planned and treated on a helical tomotherapy system. All patients had a second computed tomography scan after 15 fractions and a new plan based on this was initiated from fraction 20.ResultsRelative volume changes between computed tomography scans were: GTV 29%; CTV60 (adjuvant patients) 4%; parotid volume 17.5%; median reduction in neck separation 6–7 mm; weight loss 3%. For the group overall and for the definitively treated patient cohort, respectively, adapted plans resulted in reductions in PTV66 D₁ (0.3 Gy, P = 0.01 and 0.5 Gy, P = 0.01); PTV54 D₁ (0.6 Gy, P < 0.0001 and 0.9 Gy, P = 0.0002); spinal cord maximum (0.5 Gy, P = 0.004 and 0.6 Gy, P = 0.04) and volume of skin receiving ≥50 Gy (16 cm², P = 0.01 and 19 cm², P = 0.001). Definitively treated patients also had a reduction in mean parotid dose (0.6 Gy, P = 0.046) and volume of normal tissue receiving ≥50 Gy (67 cm³, P = 0.02). Patients with nasopharyngeal carcinoma received the greatest benefits with treatment adaptation with reduction in spinal cord maximum 1.2 Gy, mean parotid dose 1.2 Gy and parotid V₂₆ 6.3%. There was no significant benefit for adjuvant patients. Other factors associated with greater benefits were greater weight loss and greater reduction in neck separation and higher T stage.ConclusionsThere is minimal benefit to routine adaptive replanning in unselected patients, and no benefit in adjuvantly treated patients. Patients with nasopharyngeal carcinoma or with greater weight loss or reduction in neck separation did have clinically significant benefits. These patients should be targeted for adaptive strategies.