Maintenance olaparib rechallenge in patients with platinum-sensitive relapsed ovarian cancer previously treated with a PARP inhibitor (OReO/ENGOT-ov38): a phase IIIb trial.

BACKGROUND: Poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy is the standard of care for some patients with advanced ovarian cancer. We evaluated the efficacy and safety of PARP inhibitor rechallenge. PATIENTS AND METHODS: This randomized, double-blind, multicenter trial (NCT03106987) enrolled patients with platinum-sensitive relapsed ovarian cancer who had received one prior PARP inhibitor therapy for ≥18 and ≥12 months in the BRCA-mutated and non-BRCA-mutated cohorts, respectively, following first-line chemotherapy or for ≥12 and ≥6 months, respectively, following a second or subsequent line of chemotherapy. Patients were in response following their last platinum-based chemotherapy regimen and were randomized 2 : 1 to maintenance olaparib tablets 300 mg twice daily or placebo. Investigator-assessed progression-free survival (PFS) was the primary endpoint. RESULTS: Seventy four patients in the BRCA-mutated cohort were randomized to olaparib and 38 to placebo, and 72 patients in the non-BRCA-mutated cohort were randomized to olaparib and 36 to placebo; >85% of patients in both cohorts had received ≥3 prior lines of chemotherapy. In the BRCA-mutated cohort, the median PFS was 4.3 months with olaparib versus 2.8 months with placebo [hazard ratio (HR) 0.57; 95% confidence interval (CI) 0.37-0.87; P = 0.022]; 1-year PFS rates were 19% versus 0% (Kaplan-Meier estimates). In the non-BRCA-mutated cohort, median PFS was 5.3 months for olaparib versus 2.8 months for placebo (HR 0.43; 95% CI 0.26-0.71; P = 0.0023); 1-year PFS rates were 14% versus 0% (Kaplan-Meier estimates). No new safety signals were identified with olaparib rechallenge. CONCLUSIONS: In ovarian cancer patients previously treated with one prior PARP inhibitor and at least two lines of platinum-based chemotherapy, maintenance olaparib rechallenge provided a statistically significant, albeit modest, PFS improvement over placebo in both the BRCA-mutated and non-BRCA-mutated cohorts, with a proportion of patients in the maintenance olaparib rechallenge arm of both cohorts remaining progression free at 1 year.

Treatment of primary and metastatic peritoneal tumors in the Covid-19 pandemic. Proposals for prioritization from the RENAPE and BIG-RENAPE groups.

The Covid-19 pandemic is profoundly changing the organization of healthcare access. This is particularly so for peritoneal neoplastic diseases, for which curative treatment mobilizes substantial personnel, operating room and intensive care resources. The BIG-RENAPE and RENAPE groups have made tentative proposals for prioritizing care provision. A tightening of the usual selection criteria is needed for curative care: young patients with few or no comorbidities and limited peritoneal extension. It is desirable to prioritize disease conditions for which cytoreduction surgery with or without associated hyperthermic intraoperative peritoneal chemotherapy (HIPEC) is the gold-standard treatment, and for which systemic chemotherapy cannot be a temporary or long-term alternative: pseudomyxoma peritonei, resectable malignant peritoneal mesotheliomas, peritoneal metastases of colorectal origin if they are resectable and unresponsive to systemic chemotherapy after up to 12 courses, first-line ovarian carcinomatosis if resectable or in interval surgery after at most six courses of systemic chemotherapy. Addition of HIPEC must be discussed case by case in an expert center. The prioritization of indications must consider local conditions and the phase of the epidemic to allow optimal peri-operative care.

[Treatment of primary and metastatic peritoneal tumors in the Covid-19 pandemic. Proposals for prioritization from the RENAPE and BIG-RENAPE groups]. / Prise en charge des tumeurs primitives et métastatiques du péritoine en période de pandémie CoViD-19. Pistes de réflexion et de priorisation du groupe RENAPE et BIG-RENAPE.

The Covid-19 pandemic is profoundly changing the organization of healthcare access. This is particularly so for peritoneal neoplastic diseases, for which curative treatment mobilizes substantial personnel, operating room and intensive care resources. The BIG-RENAPE and RENAPE groups have made tentative proposals for prioritizing care provision. A tightening of the usual selection criteria is needed for curative care: young patients with few or no comorbidities and limited peritoneal extension. It is desirable to prioritize disease conditions for which cytoreduction surgery with or without associated hyperthermic intraoperative peritoneal chemotherapy (HIPEC) is the gold-standard treatment, and for which systemic chemotherapy cannot be a temporary or long-term alternative: pseudomyxoma peritonei, resectable malignant peritoneal mesotheliomas, peritoneal metastases of colorectal origin if they are resectable and unresponsive to systemic chemotherapy after up to 12 courses, first-line ovarian carcinomatosis if resectable or in interval surgery after at most six courses of systemic chemotherapy. Addition of HIPEC must be discussed case by case in an expert center. The prioritization of indications must consider local conditions and the phase of the epidemic to allow optimal peri-operative care.

Tumour and pelvic lymph node metabolic activity on FDG-PET/CT to stratify patients for para-aortic surgical staging in locally advanced cervical cancer.

PURPOSE: The aim of our study was to comprehensively evaluate the most valuable metabolic parameters of cervical tumours and pelvic lymph nodes (PLN) by FDG-PET/CT to predict para-aortic lymph node (PALN) metastasis and stratify patients for surgical staging. METHODS: The study included patients with locally advanced cervical cancer, negative PALN uptake on preoperative FDG-PET/CT, and para-aortic lymphadenectomy. Two senior nuclear medicine physicians expert in gynaecologic oncology reviewed all PET/CT exams, and extracted tumour SUVmax, MTV, and TLG, as well as PLN. Prognostic parameters of PALN involvement were identified using ROC curves and logistic regression analysis. RESULTS: One hundred and twenty-five consecutive locally advanced cervical cancer patients were included. The FDG-PET/CT false-negative rate was, respectively, 27.7% (13/47) and 5.1% (4/78) in patients with and without FDG-PET/CT PLN uptake. The AUC of cervical tumour size, SUVmax, MTV, and TLG was, respectively, 0.75 (0.62-0.87), 0.59 (0.44-0.76), 0.75 (0.60-0.90), and 0.71 (0.56-0.86). The AUC of PLN size, SUVmax, SUVmean, PLN SUVmax/Tumour SUVmax ratio, MTV, and TLG was, respectively, 0.57 (0.37-0.78), 0.82 (0.68-0.95), 0.77 (0.61-0.94), 0.85 (0.72-0.98), 0.69 (0.51-0.87), and 0.74 (0.57-0.91). The metabolic parameter showing the best trade-off between sensitivity and specificity to predict PALN involvement was the ratio between PLN and tumour SUVmax. CONCLUSION: The risk of PALN metastasis in FDG-PET/CT negative PLN patients is very low, so para-aortic lymphadenectomy does not seem justified. In patients with preoperative PLN uptake on FDG-PET/CT, surgical staging led to treatment modification in more than 25% of cases and should therefore be performed. Patients with more than one positive PLN and high PLN metabolic activity are at high risk of para-aortic extension and recurrence. Further prospective evaluation is required to consider intensified treatment modalities without prior PALN dissection.

Management of epithelial cancer of the ovary, fallopian tube, primary peritoneum. Long text of the joint French clinical practice guidelines issued by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY, endorsed by INCa. (Part 2: systemic, intraperitoneal treatment, elderly patients, fertility preservation, follow-up).

Adjuvant chemotherapy by carboplatin and paclitaxel is recommended for all high-grade ovarian and tubal cancers (FIGO stages I-IIA) (grade A). After primary surgery is complete, 6 cycles of intravenous chemotherapy (grade A) are recommended, or a discussion with the patient about intraperitoneal chemotherapy, according to her risk-benefit ratio. After complete interval surgery for FIGO stage III, hyperthermic intraperitoneal chemotherapy (HIPEC) can be proposed, in accordance with the modalities of the OV-HIPEC trial (grade B). In cases of postoperative tumor residue or in FIGO stage IV tumors, chemotherapy associated with bevacizumab is recommended (grade A).

Management of epithelial cancer of the ovary, fallopian tube, and primary peritoneum. Long text of the Joint French Clinical Practice Guidelines issued by FRANCOGYN, CNGOF, SFOG, and GINECO-ARCAGY, and endorsed by INCa. Part 1: Diagnostic exploration and staging, surgery, perioperative care, and pathology.

An MRI is recommended for an ovarian mass that is indeterminate on ultrasound. The ROMA score (combining CA125 and HE4) can also be calculated (grade A). In presumed early-stage ovarian or tubal cancers, the following procedures should be performed: an omentectomy (at a minimum, infracolic), an appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C), and pelvic and para-aortic lymphadenectomies (grade B) for all histologic types, except the expansile mucinous subtypes, for which lymphadenectomies can be omitted (grade C). Minimally invasive surgery is recommended for early-stage ovarian cancer, when there is no risk of tumor rupture (grade B). For FIGO stages III or IV ovarian, tubal, and primary peritoneal cancers, a contrast-enhanced computed tomography (CT) scan of the thorax/abdomen/pelvis is recommended (grade B), as well as laparoscopic exploration to take multiple biopsies (grade A) and a carcinomatosis score (Fagotti score at a minimum) (grade C) to assess the possibility of complete surgery (i.e., leaving no macroscopic tumor residue). Complete surgery by a midline laparotomy is recommended for advanced ovarian, tubal, or primary peritoneal cancer (grade B). For advanced cancers, para-aortic and pelvic lymphadenectomies are recommended when metastatic adenopathy is clinically or radiologically suspected (grade B). When adenopathy is not suspected and when complete peritoneal surgery is performed as the initial surgery for advanced cancer, the lymphadenectomies can be omitted because they do not modify either the medical treatment or overall survival (grade B). Primary surgery (before other treatment) is recommended whenever it appears possible to leave no tumor residue (grade B).

Management of epithelial cancer of the ovary, fallopian tube, and primary peritoneum. Short text of the French Clinical Practice Guidelines issued by FRANCOGYN, CNGOF, SFOG, and GINECO-ARCAGY, and endorsed by INCa.

An MRI is recommended for an ovarian mass that is indeterminate on ultrasound. The ROMA score (combining CA125 and HE4) can also be calculated (Grade A). In presumed early-stage ovarian or tubal cancers, the following procedures should be performed: an omentectomy (at a minimum, infracolic), an appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C), and pelvic and para-aortic lymphadenectomies (Grade B) for all histologic types, except the expansile mucinous subtypes, for which lymphadenectomies can be omitted (grade C). Minimally invasive surgery is recommended for early-stage ovarian cancer, when there is no risk of tumor rupture (grade B). Adjuvant chemotherapy by carboplatin and paclitaxel is recommended for all high-grade ovarian and tubal cancers (FIGO stages I-IIA) (grade A). For FIGO stage III or IV ovarian, tubal, and primary peritoneal cancers, a contrast-enhanced computed tomography (CT) scan of the thorax/abdomen/pelvis is recommended (Grade B), as well as laparoscopic exploration to take multiple biopsies (grade A) and a carcinomatosis score (Fagotti score at a minimum) (grade C) to assess the possibility of complete surgery (i.e., leaving no macroscopic tumor residue). Complete surgery by a midline laparotomy is recommended for advanced ovarian, tubal, or primary peritoneal cancers (grade B). For advanced cancers, para-aortic and pelvic lymphadenectomies are recommended when metastatic adenopathy is clinically or radiologically suspected (grade B). When adenopathy is not suspected and when complete peritoneal surgery is performed as the initial surgery for advanced cancer, the lymphadenectomies can be omitted because they do not modify either the medical treatment or overall survival (grade B). Primary surgery (before other treatment) is recommended whenever it appears possible to leave no tumor residue (grade B). After primary surgery is complete, 6 cycles of intravenous chemotherapy (grade A) are recommended, or a discussion with the patient about intraperitoneal chemotherapy, according to her risk-benefit ratio. After complete interval surgery for FIGO stage III disease, hyperthermic intraperitoneal chemotherapy (HIPEC) can be proposed, in accordance with the modalities of the OV-HIPEC trial (grade B). In cases of postoperative tumor residue or in FIGO stage IV tumors, chemotherapy associated with bevacizumab is recommended (grade A).

[Part II drafted from the short text of the French guidelines entitled "Initial management of patients with epithelial ovarian cancer" developed by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY and endorsed by INCa. (Systemic and intraperitoneal treatment, elderly, fertility preservation, follow-up)]. / Partie 2 rédigée à partir de la synthèse de la recommandation nationale de bonnes pratiques cliniques intitulée « Conduites à tenir initiales devant des patientes atteintes d'un cancer épithélial de l'ovaire ¼ élaborée par FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY et labélisée par l'INCa. (Traitement systémique et intrapéritonéal, personnes âgées, préservation de la fertilité et suivi).

Adjuvant chemotherapy with carboplatin and paclitaxel is recommended for all high-grade ovarian or Fallopian tube cancers, stage FIGO I-IIA (grade A). After a complete first surgery, it is recommended to deliver 6 cycles of intravenous (grade A) or to propose intraperitoneal (grade B) chemotherapy, to be discussed with patient, according to the benefit/risk ratio. After a complete interval surgery for a FIGO III stage, the hyperthermic intra peritoneal chemotherapy (HIPEC) can be proposed in the same conditions of the OV-HIPEC trial (grade B). In case of tumor residue after surgery or FIGO stage IV, chemotherapy associated with bevacizumab is recommended (grade A). For BRCA mutated patient, Olaparib is recommended (grade B).

[Malignant epithelial ovarian cancer: Role of intra peritoneal chemotherapy and hyperthermic intra peritoneal chemotherapy (HIPEC): Article drafted from the French Guidelines in oncology entitled "Initial management of patients with epithelial ovarian cancer" developed by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY under the aegis of CNGOF and endorsed by INCa]. / Tumeurs épithéliales malignes de l'ovaire : place de la chimiothérapie intrapéritonéale et de la chimiothérapie hyperthermique intrapéritonéale (CHIP). Article rédigé sur la base de la recommandation nationale de bonnes pratiques cliniques en cancérologie intitulée « Conduites à tenir initiales devant des patientes atteintes d'un cancer épithélial de l'ovaire ¼ élaborée par FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY sous l'égide du CNGOF et labellisée par l'INCa.

Intraperitoneal drug delivery in first-line treatment of advanced ovarian cancer have been widely studied. After a complete primary surgery or with residual disease<1cm, intraperitoneal chemotherapy significantly improves disease-free and overall survival (NP1), but with more local and systemic toxicities. Whenever this therapeutic option is under consideration, the ratio efficacy/toxicity must be carefully discussed. Intraperitoneal chemotherapy has to be considered after complete or optimal primary surgery in ovarian, tubal or primitive peritoneal carcinomatosis FIGO IIIC. This treatment must be performed by trained teams and after an assessment of the ratio efficacy/toxicity. In one randomized study, hyperthermic intraperitoneal chemotherapy (HIPEC) using cisplatinum at interval surgery demonstrated an improvement in recurrence free and overall survival compared to surgery alone, in patients initially not resectable and with residual tumor less than 1cm (complete or optimal surgery) (NP1). HIPEC has to be considered after a complete or optimal interval surgery (residu<10mm) in patients with ovarian, tubal or primitive carcinomatosis FIGO IIIC, initially not resectable (Grade B).

[Part I drafted from the short text of the French Guidelines entitled "Initial management of patients with epithelial ovarian cancer" developed by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY and endorsed by INCa. (Diagnosis management, surgery, perioperative care, and pathological analysis)]. / Partie 1 rédigée sur la base de la recommandation nationale de bonnes pratiques cliniques en cancérologie intitulée « Conduites à tenir initiales devant des patientes atteintes d'un cancer épithélial de l'ovaire ¼ élaborée par FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY et labélisée par l'INCa. (Explorations diagnostiques et bilan d'extension, chirurgie, soins périopératoires et anatomopathologie).

Faced to an undetermined ovarian mass on ultrasound, an MRI is recommended and the ROMA score (combining CA125 and HE4) can be proposed (grade A). In case of suspected early stage ovarian or fallopian tube cancer, omentectomy (at least infracolonic), appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C) and pelvic and para-aortic lymphadenectomy are recommended (grade B) for all histological types, except for the expansive mucinous subtype where lymphadenectomy may be omitted (grade C). Minimally invasive surgery is recommended for early stage ovarian cancer, if there is no risk of tumor rupture (grade B). Laparoscopic exploration for multiple biopsies (grade A) and to evaluate carcinomatosis score (at least using the Fagotti score) (grade C) are recommended to estimate the possibility of a complete surgery (i.e. no macroscopic residue). Complete medial laparotomy surgery is recommended for advanced cancers (grade B). It is recommended in advanced cancers to perform para-aortic and pelvic lymphadenectomy in case of clinical or radiological suspicion of metastatic lymph node (grade B). In the absence of clinical or radiological lymphadenopathy and in case of complete peritoneal surgery during an initial surgery for advanced cancer, it is possible not to perform a lymphadenectomy because it does not modify the medical treatment and the overall survival (grade B). Primary surgery is recommended when no tumor residue is possible (grade B).

[Uncommon dermatologic disorders triggered by radiation therapy of breast cancer: A case-series]. / Dermatoses réactionnelles rares après radiothérapie : une série de cas avec cancer du sein.

Radiotherapy's main skin toxicities are now well-separated, acute (acute radiation dermatitis) or chronic complications (chronic radiation dermatitis, induced cutaneous carcinoma, aesthetic sequelae). Exceptionally, radiotherapy may induce, by isomorphic reaction or Koebner's phenomenon, some specific dermatosis. In this article, we report five new observations of these unusual complications of radiation therapy, occurring in very variable time after breast irradiation and remaining strictly localized in the irradiated field (cutaneous mastocytosis, Sweet syndrome, lichen planus, vitiligo). These cases emphasize the need to realize a systematic histological exam if any atypical skin lesion appears after radiotherapy, even long after.

Prognostic and predictive effects of primary versus secondary platinum resistance for bevacizumab treatment for platinum-resistant ovarian cancer in the AURELIA trial.

BACKGROUND: Progression-free survival (PFS), objective response rate (ORR), and patient-reported outcomes (PROs) were significantly improved by adding bevacizumab to chemotherapy for platinum-resistant ovarian cancer (PROC) in the phase III AURELIA trial. We explored treatment outcomes according to primary platinum resistance (PPR) versus secondary platinum resistance (SPR). PATIENTS AND METHODS: Patients were categorized as PPR (disease progression <6 months after completing first-line platinum therapy) or SPR (progression ≥6 months after first platinum but <6 months after second). The exploratory Cox and logistic regression analyses correlated PFS, ORR, overall survival (OS), and PROs with the time to development of platinum resistance. RESULTS: Baseline characteristics were similar in patients with PPR (n = 262; 73%) and SPR (n = 99; 27%), although ascites were more common in the PPR subgroup. In bevacizumab-treated patients (n = 179), SPR was associated with improved PFS (median 10.2 versus 5.6 months in PPR patients; P < 0.001) and OS (median 22.2 versus 13.7 months, respectively; P < 0.001) but not PROs (22% versus 22% with improved abdominal/gastrointestinal symptoms at week 8/9). In multivariate analyses, SPR remained an independent prognostic factor for better PFS [adjusted hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.25-0.67; P < 0.001] and OS (HR 0.49, 95% CI 0.30-0.80; P = 0.005) in bevacizumab-treated patients, but was not statistically significant for either end point in the chemotherapy-alone subgroup. The magnitude of PFS benefit from bevacizumab appeared greater in SPR than PPR patients (HR 0.30 versus 0.55, respectively; interaction P = 0.07) with a similar direction of effect for OS (interaction P = 0.18). CONCLUSIONS: In bevacizumab-treated patients, PFS and OS were more favorable in SPR than PPR patients with equally improved PROs. The PFS and OS benefit from combining bevacizumab with chemotherapy was more pronounced in SPR than PPR PROC. PPR versus SPR should be a stratification factor in future trials evaluating anti-angiogenic therapy for PROC.

Professional risks when carrying out cytoreductive surgery for peritoneal malignancy with hyperthermic intraperitoneal chemotherapy (HIPEC): A French multicentric survey.

BACKGROUND: Over the last two decades, many surgical teams have developed programs to treat peritoneal carcinomatosis with extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). Currently, there are no specific recommendations for HIPEC procedures concerning environmental contamination risk management, personal protective equipment (PPE), or occupational health supervision. METHODS: A survey of the institutional practices among all French teams currently performing HIPEC procedures was carried out via the French network for the treatment of rare peritoneal malignancies (RENAPE). RESULTS: Thirty three surgical teams responded, 14 (42.4%) which reported more than 10 years of HIPEC experience. Some practices were widespread, such as using HIPEC machine approved by the European Community (100%), individualized or centralized smoke evacuation (81.8%), "open" abdominal coverage during perfusion (75.8%), and maintaining the same surgeon throughout the procedure (69.7%). Others were more heterogeneous, including laminar flow air circulation (54.5%) and the provision of safety protocols in the event of perfusate spills (51.5%). The use of specialized personal protective equipment is ubiquitous (93.9%) but widely variable between programs. CONCLUSION: Protocols regarding cytoreductive surgery/HIPEC and the associated professional risks in France lack standardization and should be established.

Quality indicators in ovarian cancer surgery: report from the French Society of Gynecologic Oncology (Societe Francaise d'Oncologie Gynecologique, SFOG).

BACKGROUND: Based on registries, the European experience has been that <50% of patients are treated according to protocols and/or benefit from the minimum required surgery for ovarian cancer. The French Cancer Plan 2009-2013 considers the definition of qualitative indicators in ovarian cancer surgery in France. This endeavour was undertaken by the French Society of Gynaecologic Oncology (SFOG) in partnership with the French National College of Obstetricians and Gynecologists and all concerned learned societies in a multidisciplinary mindset. METHODS: The quality indicators for the initial management of patients with ovarian cancer were based on the standards of practice determined from scientific evidence or expert consensus. RESULTS: The indicators were divided into structural indicators, including material (equipment), human (number and qualification of staff), and organizational resources, process indicators, and outcome indicators. CONCLUSIONS: The enforcement of a quality assurance programme in any country would undoubtedly promote improvement in the quality of care for ovarian cancer patients and would result in a dramatic positive impact on their survival. Such a policy is not only beneficial to the patient, but is also profitable for the healthcare system.

A randomized clinical trial of adjuvant chemotherapy with doxorubicin, ifosfamide, and cisplatin followed by radiotherapy versus radiotherapy alone in patients with localized uterine sarcomas (SARCGYN study). A study of the French Sarcoma Group.

BACKGROUND: There is no proven benefit of adjuvant treatment of uterine sarcoma (US). SARCGYN phase III study compared adjuvant polychemotherapy followed by pelvic radiotherapy (RT) (arm A) versus RT alone (arm B) conducted to detect an increase ≥ 20% of 3-year PFS. METHODS: Patients with FIGO stage ≤ III US, physiological age ≤ 65 years; chemotherapy: four cycles of doxorubicin 50 mg/m² d1, ifosfamide 3 g/m²/day d1-2, cisplatin 75 mg/m² d3, (API) + G-CSF q 3 weeks. Study was stopped because of lack of recruitment. RESULTS: Eighty-one patients were included: 39 in arm A and 42 in arm B; 52 stage I, 16 stage II, 13 stage III; 53 leiomyosarcomas, 9 undifferenciated sarcomas, 19 carcinosarcomas. Gr 3-4 toxicity during API (/37 patients): thrombopenia (76%), febrile neutropenia (22%) with two toxic deaths; renal gr 3 (1 patient). After a median follow-up of 4.3 years, 41/81 patients recurred, 15 in arm A, 26 in arm B. The 3 years DFS is 55% in arm A, 41% in arm B (P = 0.048). The 3-year overall survival (OS) is 81% in arm A and 69% in arm B (P = 0.41). CONCLUSION: API adjuvant CT statistically increases the 3 year-DFS of patients with US.

Combined oral topotecan plus carboplatin in relapsed or advanced cervical cancer: a GINECO phase I-II trial.

AIM: Combined cisplatin-topotecan therapy is standard care for advanced cervical cancer, however it is associated with haematotoxicity and nephrotoxicity. This trial was designed to assess the combination of carboplatin which is less nephrotoxic, and oral topotecan. PATIENTS AND METHODS: Patients with advanced/recurrent squamous cervical cancer received carboplatin (AUC5) on day 1, with escalating oral topotecan (3.0 mg/m(2) starting dose) on days 1, 8 and 15, every 4 weeks. Endpoints were the maximal tolerated dose for the phase I part and safety profiles and response rates for the phase II part of the study. RESULTS: Two dose levels were evaluated. A total of 18 patients (6 phase I, 12 phase II) were treated. The maximal tolerated dose was 3.0 mg/m(2) topotecan with carboplatin AUC5. Phase II accrual was interrupted following unacceptable toxicity, with 10 therapy-related related serious events in 9 out of 12 patients: grade 3-4 pancytopenia (7), febrile neutropenia (1), grade 3 haemorrhage (1) and grade 3 vomiting (1). CONCLUSION: Weekly oral topotecan combined with carboplatin is associated with unmanageable toxicity and is not recommended. Future studies are warranted to better understand the toxicity of such a combination and explore alternative combinations for advanced cervical cancer.

French women's breast self-examination practices with time after undergoing BRCA1/2 genetic testing.

To assess the impact of BRCA1/2 genetic test results on cancer-free women's breast-self-examination (BSE) practices and to prospectively determine their influence on psychological functioning. A prospective longitudinal study on French women's BSE practices and frequencies in BRCA1/2 carriers (N = 217) and non-carriers (N = 313) 1 and 2 years following disclosure of the test results, along with psychological factors predicting BSE practices. Before disclosure, BSE was practised by 47.2% of the women, and increased to 57.3% 1 year later. No change in the women's practices was noted between 12 and 24 months after the test. Carriers and non-carriers practicing regularly BSE at baseline were, respectively 8 to 6 times more likely to be practising BSE regularly at 12 months after being tested. Among the carriers, having fewer depressive symptoms at baseline and believing in the ability of BSE to detect breast cancer were found to be the most decisive factors associated with BSE practices 1 year after disclosure, following adjustment for BSE baseline practices. Among the non-carriers, believing in the ability of BSE to detect breast cancer, greater post-test anxiety, and a higher perceived risk of breast cancer were found to be predictors of post-test BSE practices after adjusting for BSE baseline practices. In France, where performing BSE is neither mandatory nor recommended, an increase in BSE practices was found to occur after disclosure of women's genetic test results, regardless of their carrier status.

Weekly paclitaxel as a single agent or in combination with carboplatin or weekly topotecan in patients with resistant ovarian cancer: the CARTAXHY randomized phase II trial from Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO).

BACKGROUND: Platinum rechallenge or weekly topotecan in combination have not been evaluated in randomized trials for resistant recurrent ovarian cancer (ROC). METHODS: Patients with ROC after first- or second-line treatment including a platinum and taxane and progression within 6 months were randomized to weekly paclitaxel (wP, 80 mg/m(2)/week) alone or in combination with carboplatin (C, area under the curve of 5 mg/ml/min every 4 weeks) or weekly topotecan (wT, 3 mg/m(2)/week). Primary end point was progression-free survival (PFS) comparing wP and combination therapy. RESULTS: Patients (n = 165) received a median three cycles in each arm. Nonhematologic toxicity was not different, except increased hypersensitivity reactions with wP + C. Grade 3-4 hematologic toxic effects with wP, wP + C, and wP + wT, respectively, were neutropenia in 13%, 54%, and 42%; febrile neutropenia in 0%, 4%, and 5%; and anemia in 6%, 19%, and 29%. Response rates were 35%, 37%, and 39%, and median PFS times were 3.7, 4.8, and 5.4 months, respectively. PFS was not significantly different among the treatment arms [hazard ratio (HR) 0.922; 95% confidence interval (CI) 0.765-1.111; P = 0.46] or between monotherapy and combination therapy (HR 0.951; 95% CI 0.686-1.318; P = 0.76). CONCLUSIONS: Combination chemotherapy in platinum-resistant ROC was more toxic than weekly paclitaxel and did not significantly prolong PFS.

Carboplatin and pegylated liposomal doxorubicin versus carboplatin and paclitaxel in partially platinum-sensitive ovarian cancer patients: results from a subset analysis of the CALYPSO phase III trial.

BACKGROUND: To perform a subset analysis of patients with partially platinum-sensitive recurrent ovarian cancer (ROC) who received either CD [carboplatin-pegylated liposomal doxorubicin (PLD)] or CP (carboplatin-paclitaxel) in the CALYPSO trial. PATIENTS AND METHODS: CALYPSO, an international phase III, non-inferiority trial, enrolled women with ROC that relapsed >6 months following first- or second-line therapy. Patients were randomized to CD or CP. Patients with a treatment-free interval of >6 and ≤ 12 months were evaluated for progression-free survival (PFS), the primary end point of CALYPSO trial, and safety. RESULTS: A total of 344 partially platinum-sensitive patients were included (N = 161, CD and N = 183, CP). The hazard ratio for PFS was 0.73 (95% confidence interval: 0.58-0.90; P = 0.004 for superiority) in favor of CD. Median PFS times were 9.4 months (CD) and 8.8 months (CP). Toxicities more common with CP versus CD included grade 3/4 neutropenia (50% versus 39%; P = 0.015), grade 2 alopecia (86% versus 9%; P < 0.001), neuropathy and hypersensitivity reactions. Hand-foot syndrome was more common with CD; however, grade 3/4 reactions were low (one patient in each arm). CONCLUSION: Carboplatin-PLD has a more favorable risk-benefit profile than CP in patients with partially platinum-sensitive ROC and should be considered an effective treatment option for these patients.