ABSTRACT
The imaging has critical responsibility in the assessment of peritoneal lesions along with estimating the overall extent. Valuing disease burden is crucial for selection of combining cytoreductive surgery (CRS) and intraperitoneal hyperthermic chemotherapy (HIPEC) treatment. An approach that combines the strength of several imaging tools and increases diagnostic accuracy, should be chosen, even if the preferred imaging tool in patients with suspected Peritoneal Carcinomatosis (PC) is CT. The outcomes of PC are mainly correlated to tumor spread, localization, and lesion size. Accurate assessment of these features is critical for prognosis and treatment planning. These data can be evaluated by Peritoneal Cancer Index (PCI), a quantitative index suggested by Harman and Sugarbaker. Additionally, precise predictive biomarkers should be established to predict PC in patients at risk. The radiomics analysis could predict PC throughout the evaluation of cancers heterogeneity.
Subject(s)
Hyperthermia, Induced , Peritoneal Neoplasms , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Combined Modality Therapy , Cytoreduction Surgical Procedures , Humans , Hyperthermia, Induced/methods , Hyperthermic Intraperitoneal Chemotherapy , Peritoneal Neoplasms/diagnostic imaging , Peritoneal Neoplasms/therapyABSTRACT
OBJECTIVE: To assess predictors of recurrence following laparoscopic radical hysterectomy (LRH) for apparent early stage cervical cancer (CC). METHODS: This is a retrospective multi-institutional study reviewing data of consecutive patients who underwent LRH for FIGO 2009 stage IA1 (with lymphovascular space invasion (LVSI)), IA2 and IB1(≤4 cm) CC, between January 2006 and December 2017. The following histotypes were included: squamous, adenosquamous, and adenocarcinoma. Multivariable models were used to estimate adjusted odds ratio (OR) and corresponding 95% CI. Factors influencing disease-free survival (DFS) and disease-specific survival (DSS) were also explored. RESULTS: 428 patients were included in the analysis. With a median follow-up of 56 months (1-162) 54 patients recurred (12.6%). At multivariable analysis, tumor size (OR:1.04, 95%CI:1.01-1.09, p = .02), and presence of cervical residual tumor at final pathology (OR: 5.29, 95%CI:1.34-20.76, p = .02) were found as predictors of recurrence; conversely preoperative conization reduced the risk (OR:0.32, 95%CI:0.11-0.90, p = .03). These predictors remained significant also in the IB1 subgroup: tumor size: OR:1.05, 95%CI:1.01-1.09, p = .01; residual tumor at final pathology: OR: 6.26, 95%CI:1.58-24.83, p = .01; preoperative conization: OR:0.33, 95%CI:0.12-0.95, p = .04. Preoperative conization (HR: 0.29, 95%CI: 0.13-0.91; p = .03) and the presence of residual tumor on the cervix at the time of surgery (HR: 8.89; 95%CI: 1.39-17.23; p = .01) independently correlated with DFS. No independent factors were associated with DSS. CONCLUSIONS: In women with early stage CC the presence of high-volume disease at time of surgery represent an independent predictor of recurrence after LRH. Conversely, preoperative conization and the absence of residual disease at the time of surgery might play a protective role.
Subject(s)
Cervix Uteri/pathology , Hysterectomy/adverse effects , Laparoscopy/adverse effects , Neoplasm Recurrence, Local/epidemiology , Postoperative Complications/epidemiology , Uterine Cervical Neoplasms/surgery , Adult , Cervix Uteri/surgery , Conization/statistics & numerical data , Disease-Free Survival , Female , Follow-Up Studies , Humans , Hysterectomy/methods , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/prevention & control , Neoplasm Staging , Neoplasm, Residual , Postoperative Complications/etiology , Preoperative Care/statistics & numerical data , Protective Factors , Retrospective Studies , Risk Assessment/methods , Risk Assessment/statistics & numerical data , Risk Factors , Tumor Burden , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/mortality , Uterine Cervical Neoplasms/pathologyABSTRACT
PURPOSE: To evaluate the practice patterns among centers and physicians worldwide regarding sentinel lymph node biopsies (SLNB) in cervical cancer (CC) patients. METHOD: A validated 35-item questionnaire regarding SLNB in CC supported by the Gynecologic Cancer Intergroup (GCIG), and sponsored by the North-Eastern German Society of Gynaecologic-Oncology (NOGGO) was sent to all major gynecological cancer societies across the globe for further distribution from October 2015 and continued for a period of 7 months. RESULTS: One hundred and sixty-one institutions from around the world participated. One hundred and six (66%) of the participants were from university centers and 111 (69%) were gynecologic oncologists. One hundred and fifty-two (97%) performed lymphadenectomy (LNE) and 147 (94%) did so systematically; 97 (60%) used SLNB, due to lower morbidity (73%), reliability (55%) and time-saving (27%). In cases of positive SLNB (pN+), 39% of respondents stopped the operation and sent the patient for chemoradiation (CRT), 45% completed pelvic and paraaortic LNE, whereas 26% went on to perform a radical hysterectomy (RH) and systematic pelvic and paraaortic LNE. In case of negative SLNB (pN0), 39% of institutions still performed a systematic pelvic and paraaortic LNE. CONCLUSION: In this survey worldwide, SLNB adoption is an encouraging 60%, yet ample differences exist regarding strategy, and to a lower extent the techniques used. Lack of experience is the most common reason SLNB is not performed. Efforts to increase surgical education on SLNB technique and multicenter prospective trials providing evidence-based guidelines are warranted.
Subject(s)
Sentinel Lymph Node Biopsy/methods , Uterine Cervical Neoplasms/surgery , Female , Humans , Middle Aged , Prospective Studies , Surveys and Questionnaires , Uterine Cervical Neoplasms/pathologyABSTRACT
OBJECTIVES: To evaluate the impact of tertiary cytoreductive surgery (TCS) on survival in recurrent epithelial ovarian cancer (EOC), and to determine predictors of complete cytoreduction. METHODS: A multi-institutional retrospective study was conducted within the MITO Group on a 5-year observation period. RESULTS: A total of 103 EOC patients with a ≥6month treatment-free interval (TFI) undergoing TCS were included. Complete cytoreduction was achieved in 71 patients (68.9%), with severe post-operative complications in 9.7%, and no cases of mortality within 60days from surgery. Multivariate analysis identified the complete tertiary cytoreduction as the most potent predictor of survival followed by FIGO stage I-II at initial diagnosis, exclusive retroperitoneal recurrence, and TCS performed ≥3years after primary diagnosis. Patients with complete tertiary cytoreduction had a significantly longer overall survival (median OS: 43months, 95% CI 31-58) compared to those with residual tumor (median OS: 33months, 95% CI 28-46; p<0.001). After multivariate adjustment the presence of a single lesion and good (ECOG 0) performance status were the only significant predictors of complete surgical cytoreduction. CONCLUSIONS: This is the only large multicentre study published so far on TCS in EOC with ≥6month TFI. The achievement of postoperative no residual disease is confirmed as the primary objective also in a TCS setting, with significant survival benefit and acceptable morbidity. Accurate patient selection is of utmost importance to have the best chance of complete cytoreduction.
Subject(s)
Cytoreduction Surgical Procedures/methods , Neoplasm Recurrence, Local/surgery , Neoplasms, Glandular and Epithelial/surgery , Ovarian Neoplasms/surgery , Adult , Aged , Carcinoma, Ovarian Epithelial , Female , Humans , Middle Aged , Multivariate Analysis , Neoplasm Recurrence, Local/pathology , Neoplasms, Glandular and Epithelial/mortality , Ovarian Neoplasms/mortality , Retrospective Studies , Risk Factors , Young AdultABSTRACT
INTRODUCTION: Chemotherapy is the standard treatment of recurrent epithelial ovarian cancer (EOC), but its use in nodal relapses is still debated. On the other hand, the role of secondary cytoreductive surgery (SCS) remains controversial. Aim of this study is to evaluate feasibility and outcomes of SCS for the specific setting of recurrent ovarian cancer, exclusively relapsing in lymph nodes. PATIENTS AND METHODS: We conducted a retrospective analysis in five Italian Institutions (University of Torino, INT of Milano, CRO of Aviano, University of Pisa and INT of Napoli) from 2000 to 2012. Patients with EOC who underwent secondary surgery for isolated lymph node recurrence (ILNR) were selected. RESULTS: Seventy-three patients were identified. At first diagnosis, patients received debulking surgery and platinum-based chemotherapy. The median disease free interval from completion of primary chemotherapy to nodal recurrence was 18 months. Nodal recurrence was para-aortic in 37 patients (50.7%), pelvic in 21 (28.8%), pelvic and para-aortic in 9 (12.3%), pelvic and inguinal in 3 (4.1%) and inguinal in 3 (4.1%). During SCS, in 1 patients nephrectomy was necessary for renal vein injury. No significant postoperative morbidity occurred. Median follow-up is 50 months. After secondary surgery, 32 (43.8%) are alive without disease, 18 (24.6%) are alive with disease and 23 patients (31.5%) are dead of disease. Five-year overall survival from the time of treatment of recurrent disease is 64%. CONCLUSIONS: Secondary surgery for ILNR of ovarian cancer is feasible, safe, with low morbidity and it is associated with a favorable outcome.
Subject(s)
Lymph Nodes/pathology , Neoplasm Recurrence, Local/surgery , Neoplasms, Glandular and Epithelial/secondary , Neoplasms, Glandular and Epithelial/therapy , Ovarian Neoplasms/pathology , Ovarian Neoplasms/therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Ovarian Epithelial , Chemotherapy, Adjuvant , Cohort Studies , Combined Modality Therapy , Disease-Free Survival , Female , Follow-Up Studies , Humans , Italy , Lymph Node Excision/methods , Lymph Nodes/surgery , Lymphatic Metastasis , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasms, Glandular and Epithelial/mortality , Ovarian Neoplasms/mortality , Ovarian Neoplasms/secondary , Ovariectomy/methods , Reoperation/methods , Retrospective Studies , Risk Assessment , Survival Analysis , Treatment OutcomeABSTRACT
OBJECTIVE: Human papillomavirus (HPV) genotypes have been extensively studied in uterine cervix squamous cell carcinoma and HPV16 variants have been found to be associated with increased cancer risk, but few reports have been published on genotype distribution and HPV16 variant prevalence in adenocarcinoma tumors. The objective of this study was to analyze viral genotypes and HPV16 intratypic variants in cervical adenocarcinoma and squamous cell carcinoma of Italian women. METHODS: A total of 39 invasive adenocarcinoma and 132 squamous cell carcinoma were reviewed and classified according to the modified WHO classification. HPV sequences were detected by nested PCR, using the broad spectrum consensus-primer pairs MY09/MY11 and the GP5+/GP6+ system, and genotyped by nucleotide sequence analysis. The HPV16-positive cases were amplified with E6-specific oligonucleotides and amplimers subjected to direct nucleotide sequence for variant identification. RESULTS: The prevalence rate of any HPV infection was 72% in adenocarcinoma, and 85% in cervical squamous cell carcinoma. Among the 140 HPV-positive cancer cases, a total of nine mucosal HPV genotypes (HPV16, 18, 31, 33, 35, 39, 45, 58, 82) epidemiologically classified as carcinogenic or probably carcinogenic viruses were identified. The HPV type 16 was the most common viral type representing 64% and 73% of all infections in adenocarcinoma and squamous cell carcinoma, respectively. The E6 nucleotide sequence analysis of HPV16 isolates allowed the identification of Asian American (AA) variants in 33% of adenocarcinoma and in 20% of squamous cell carcinoma suggesting their stronger association with cancer of glandular origin. CONCLUSION: These results suggest that HPV16 has a high prevalence in both invasive adenocarcinoma and squamous cell carcinoma from Italian patients. Moreover this study confirms previous observations, summarized in a systematic review of the literature, on the increased cancer risk of HPV16 AA class in adenoglandular cancer, possibly related to their more oncogenic behavior compared to HPV16 European variants.
Subject(s)
Adenocarcinoma/virology , Carcinoma, Squamous Cell/virology , Human papillomavirus 16/genetics , Papillomavirus Infections/virology , Uterine Cervical Neoplasms/virology , Adenocarcinoma/epidemiology , Carcinoma, Squamous Cell/epidemiology , Female , Genotype , Human papillomavirus 16/classification , Human papillomavirus 16/isolation & purification , Humans , Italy/epidemiology , Papillomavirus Infections/complications , Papillomavirus Infections/epidemiology , Polymerase Chain Reaction , Uterine Cervical Neoplasms/epidemiologyABSTRACT
OBJECTIVE: To determine the sensitivity and specificity of the 'ovarian crescent sign' (OCS)-a rim of normal ovarian tissue seen adjacent to an ipsilateral adnexal mass-as a sonographic feature to discriminate between benign and malignant adnexal masses. METHODS: The patients included were a subgroup of patients participating in the International Ovarian Tumor Analysis (IOTA) Phase 2 study, which is an international multicenter study. The subgroup comprised 1938 patients, with an adnexal mass, recruited from 19 ultrasound centers in different countries. All patients were scanned using the same standardized ultrasound protocol. Information on more than 40 demographic and ultrasound variables were collected, but the evaluation of the OCS was optional. Only patients from centers that had evaluated the OCS in > or = 90% of their cases were included. The gold standard was the histological diagnosis of the adnexal mass. The ability of the OCS to discriminate between borderline or invasively malignant vs. benign adnexal masses, as well as between invasively malignant vs. other (benign and borderline) tumors, was determined and compared with the performance of subjective evaluation of ultrasound findings by the ultrasound examiner. RESULTS: The OCS was evaluated in 1377 adnexal masses from 12 centers, 938 (68%) masses being benign, 86 (6%) borderline, 305 (22%) primary invasive and 48 (3%) metastases. The OCS was present in 398 (42%) of 938 benign masses, in 14 (16%) of 86 borderline tumors, in 18 (6%) of 305 primary invasive tumors (one malignant struma ovarii, one uterine clear cell adenocarcinoma and 16 epithelial carcinomas, i.e. four Stage I and 12 Stage II-IV) and in two (4%) of 48 ovarian metastases. Hence, the sensitivity and specificity for absent OCS to identify a malignancy was 92% and 42%, respectively, and the positive and negative likelihood ratios (LR+ and LR-, respectively) were 1.60 and 0.18. Subjective impression performed significantly better than the OCS. Sensitivity and specificity were 90% and 92%, respectively, LR+ was 11.0 and LR- was 0.10. For discrimination between invasive vs. benign or borderline tumors, the sensitivity for absent OCS was 94%, the specificity was 40%, the LR+ was 1.58 and the LR- was 0.14. CONCLUSION: This study confirms previous reports that the presence of the OCS decreases the likelihood of invasive malignancy in adnexal masses. However it is a poor discriminator between benign and malignant adnexal masses.
Subject(s)
Ovarian Neoplasms/diagnostic imaging , Ovary/diagnostic imaging , Adnexal Diseases/diagnostic imaging , Diagnosis, Differential , Female , Humans , Neoplasm Staging , Predictive Value of Tests , Prospective Studies , Sensitivity and Specificity , Ultrasonography, DopplerABSTRACT
BACKGROUND: There is some evidence that dietary habits may influence the risk of endometrial cancer independently of body mass, although the role of diet on endometrial carcinogenesis is unclear. PATIENTS AND METHODS: We carried out a multicenter case-control study from 1992 to 2006 in Italy on 454 women with incident, histologically confirmed endometrial cancer (age range 18-79 years) and 908 controls (age range 19-79 years) admitted to hospitals for acute, non-neoplastic diseases. A validated food-frequency questionnaire was used to estimate macronutrients, fatty acids and cholesterol intake. Logistic regression models, conditioned on age and study centre, and adjusted for major known risk factor of endometrial cancer and residual of energy intake were used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Significant direct associations were observed with intake of energy (OR = 1.7 for the highest versus the lowest quintile, 95% CI = 1.1-2.5), and cholesterol (OR = 2.1, 95% CI = 1.4-3.2), while a direct borderline association emerged with saturated fatty acids (OR = 1.3, 95% CI = 0.9-2.0). There was no association with proteins, sugars, starch, total fat and other selected fatty acids. CONCLUSION: Energy and cholesterol intake were associated with endometrial cancer.
Subject(s)
Cholesterol, Dietary/adverse effects , Diet/statistics & numerical data , Endometrial Neoplasms/epidemiology , Energy Intake , Adolescent , Adult , Aged , Body Mass Index , Case-Control Studies , Comorbidity , Diet/adverse effects , Dietary Carbohydrates , Dietary Fats , Dietary Proteins , Disease Susceptibility , Endometrial Neoplasms/etiology , Estrogens/adverse effects , Feeding Behavior , Female , Humans , Italy/epidemiology , Middle Aged , Risk FactorsABSTRACT
Anthracyclines and platinum derivates are active drugs for advanced endometrial carcinoma (AEC), but new schedules with higher efficacy and better tolerability are needed. A phase II study was conducted to describe activity and tolerability of carboplatin (C)+pegylated liposomal doxorubicin (PLD) in patients with AEC. Patients with chemonaive AEC, PS < or = 2, aged < 75 years, with at least one measurable lesion were eligible. Treatment was C (area under curve 5)+PLD (40 mg m(-2)) on day 1 every 4 weeks, up to six cycles. Forty-two patients were needed in a single-stage design, with at least 13 objective responses to define the treatment active. Forty-two patients were enrolled. Median age was 64 years (31-74). A total of 64% of patients were recurrent while 36% were advanced. Three complete (7%) and 22 partial responses (52%) were observed, for an overall response rate of 59.5% (95% exact CI: 43.3-74.3). One death potentially related to treatment was recorded (death at home for unknown reasons after 6th cycle). Other relevant toxicities (% of patients) were grade 3/4 neutropaenia 33%/14%, febrile neutropaenia 5%, grade 3/4 thrombocytopaenia 17%/5%, grade 3/4 anaemia 31%/2%. Skin toxicity was mild: grade 1 14%, grade 2 10%, grade 3 5%. Hair loss: complete 5%, partial 12%. The combination of carboplatin and PLD shows good activity and favourable toxicity as first-line chemotherapy of patients with AEC, deserving further studies in this setting.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/administration & dosage , Carcinoma, Endometrioid/drug therapy , Doxorubicin/analogs & derivatives , Endometrial Neoplasms/drug therapy , Polyethylene Glycols/administration & dosage , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/adverse effects , Carcinoma, Endometrioid/pathology , Disease Progression , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Endometrial Neoplasms/pathology , Female , Humans , Italy , Middle Aged , Neoadjuvant Therapy/adverse effects , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/drug therapy , Polyethylene Glycols/adverse effectsABSTRACT
No randomised trials have addressed the value of systematic aortic and pelvic lymphadenectomy (SL) in ovarian cancer macroscopically confined to the pelvis. This study was conducted to investigate the role of SL compared with lymph nodes sampling (CONTROL) in the management of early stage ovarian cancer. A total of 268 eligible patients with macroscopically intrapelvic ovarian carcinoma were randomised to SL (N=138) or CONTROL (N=130). The primary objective was to compare the proportion of patients with retroperitoneal nodal involvement between the two groups. Median operating time was longer and more patients required blood transfusions in the SL arm than the CONTROL arm (240 vs 150 min, P<0.001, and 36 vs 22%, P=0.012, respectively). More patients in the SL group had positive nodes at histologic examination than patients on CONTROL (9 vs 22%, P=0.007). Postoperative chemotherapy was delivered in 66% and 51% of patients with negative nodes on CONTROL and SL, respectively (P=0.03). At a median follow-up of 87.8 months, the adjusted risks for progression (hazard ratio [HR]=0.72, 95%CI=0.46-1.21, P=0.16) and death (HR=0.85, 95%CI=0.49-1.47, P=0.56) were lower, but not statistically significant, in the SL than the CONTROL arm. Five-year progression-free survival was 71.3 and 78.3% (difference=7.0%, 95% CI=-3.4-14.3%) and 5-year overall survival was 81.3 and 84.2% (difference=2.9%, 95% CI=-7.0-9.2%) respectively for CONTROL and SL. SL detects a higher proportion of patients with metastatic lymph nodes. This trial may have lacked power to exclude clinically important effects of SL on progression free and overall survival.
Subject(s)
Lymph Node Excision , Ovarian Neoplasms/surgery , Pelvic Neoplasms/surgery , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Adjuvant , Disease Progression , Female , Humans , Lymph Nodes/pathology , Lymph Nodes/surgery , Lymphatic Metastasis , Middle Aged , Neoplasm Staging , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Pelvic Neoplasms/drug therapy , Pelvic Neoplasms/pathology , Risk Factors , Survival Rate , Treatment OutcomeABSTRACT
Epidemiologic analysis reveals that mortality rates from ovarian cancer are continuously decreasing due to the improvement of surgery and chemotherapy. However, overall, the prognosis of ovarian cancer patients is still unsatisfactory considering that only 30% of the patients are alive after 5 years. In fact, although surgery and first-line systemic chemotherapy induce complete and partial response in up to 80% of patients, with about a 25% pathological complete remission rate, recurrences occur in the majority of patients. Most of these patients are subject to repetitive treatment cycles that, although palliative in nature, are also able to prolong survival. Important results have been obtained, in particular in platinum sensitive recurrent disease where a platinum base chemotherapy is able to prolong progression-free survival and overall survival. Overall, our armamentarium for the treatment of progressive or recurrent ovarian cancer is significantly richer than in the past, and in many patients it is possible to achieve the objective to reach a chronic history of the disease.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/drug therapy , Female , Humans , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/pharmacologyABSTRACT
BACKGROUND: The aim of this study was to determine the maximum tolerated dose (MTD) of liposomal doxorubicin (LD)-vinorelbine (V) in patients with refractory or resistant ovarian cancer. PATIENTS AND METHODS: Thirty patients were eligible. Seven levels were studied [LD 25-V20 (three patients enrolled); LD 30-V20 (three); LD 35-V20 (three); LD 20-V25 (three); LD 25-V25 (three); LD 30-V25 (10); LD 35-V25 (five)]. LD was given on day 1, while V was given on days 1 and 8 every 21 days. Cohorts of three patients were enrolled at each level, and another three patients were planned, if one dose-limiting toxicity (DLT) was registered. RESULTS: DLT was observed in four patients: two febrile neutropenia, one grade 4 thrombocytopenia and one grade 3 palmar-plantar erythrodysesthesia (PPE) at level 7 (LD 35-V25). Thus, liposomal doxorubicin 30 mg/m(2) plus vinorelbine 25 mg/m(2) was the MTD. The most frequent toxicity was neutropenia. Fifteen patients (50%) experienced grade 3 neutropenia and 10 (33.3%) grade 4 neutropenia. Non-hematological toxicity was mild. Mucositis and PPE were the most frequent toxicities, but in most cases were grade 1. Out of 29 assessable patients, six (20.7%; 95% confidence interval 10%-39%) experienced an objective response, with one complete response. CONCLUSIONS: In patients with refractory or resistant ovarian cancer, the recommended doses for the combination studied are liposomal doxorubicin 30 mg/m(2) (day 1) plus vinorelbine 25 mg/m(2) (day 1 and 8). Neutropenia is the most frequent toxicity, while non-hematological toxicity is mild. Substantial activity was recorded and a phase II study is justified.
Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Doxorubicin/administration & dosage , Epithelial Cells/pathology , Ovarian Neoplasms/drug therapy , Vinblastine/analogs & derivatives , Vinblastine/administration & dosage , Adult , Aged , Antibiotics, Antineoplastic/adverse effects , Antibiotics, Antineoplastic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cohort Studies , Dose-Response Relationship, Drug , Doxorubicin/adverse effects , Doxorubicin/therapeutic use , Drug Resistance, Neoplasm , Female , Humans , Liposomes , Maximum Tolerated Dose , Middle Aged , Vinblastine/adverse effects , Vinblastine/therapeutic use , VinorelbineABSTRACT
BACKGROUND: Carboplatin is a milestone drug against ovarian carcinoma; it is used both in front-line and second-line chemotherapy. Hypersensitivity reactions to carboplatin may occur during the treatment as salvage therapy. The purpose of this study was to describe the feasibility of the replacing of carboplatin with cisplatin in patients presenting with severe hypersensitivity reactions to carboplatin. PATIENTS AND METHODS: Ten consecutive patients with platinum-sensitive, recurrent ovarian carcinoma, presenting with moderate/severe hypersensitivity reactions to carboplatin were treated with cisplatin 60 mg/m2 from January 2000 to December 2002. Hypersensitivity reactions consisted of respiratory distress (chest tightness, wheezing, dyspnea), urticaria/erythema with tachycardia, facial swelling and hypotension. RESULTS: The total number of cisplatin cycles given was 44 (range 2-5). The treatment with cisplatin was generally well tolerated. No serious allergic reactions occurred. A mild allergic reaction was recorded (urticaria) in only one case, after one cycle of cisplatin, and the patient was not rechallenged because of progressive disease. No reductions of chemotherapy doses were needed. CONCLUSION: To date, platinum-based regimens remain the most effective treatment in recurrent platinum-sensitive ovarian cancer with a high rate of objective responses. Although our experience is limited, we suggest that, under anesthesiologic surveillance and providing immunologic blockade, the replacement of carboplatin salvage therapy with cisplatin can be considered a safe therapeutic strategy in patients who cannot continue carboplatin due to allergic reactions.
Subject(s)
Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Carboplatin/adverse effects , Cisplatin/therapeutic use , Drug Hypersensitivity/etiology , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/drug therapy , Aged , Carboplatin/therapeutic use , Cisplatin/adverse effects , Female , Humans , Middle Aged , Neoplasm Recurrence, Local/immunology , Ovarian Neoplasms/immunology , Salvage TherapyABSTRACT
BACKGROUND: A phase III multicenter randomized trial has been designed in order to address whether amifostine (WR-2721, Ethyol), an organic thiophosphate cytoprotector, can protect ovarian cancer patients from toxicity induced by carboplatin-paclitaxel chemotherapy. PATIENTS AND METHODS: Patients were randomly assigned to receive carboplatin [area under the curve (AUC) 5 mg.min/ml] and paclitaxel (175 mg/m(2)) with (arm A) or without (arm B) amifostine (910 mg/m(2)) every 21 days for six cycles. RESULTS: One-hundred and eighty-seven patients were accrued: 93 patients in arm A and 94 patients in arm B. There was no difference in terms of erythrocytopenia between the two arms; grade 3-4 thrombocytopenia was higher in arm A (3.3% versus 0.6%; P = 0.0010). There was no significant reduction of grade 3-4 leukopenia in arm A (11.8% versus 13.8%). The incidence of grade 3-4 neutropenia was lower in arm A (31.3% versus 37.9%; P = 0.03), as was the incidence of severe mucositis (4.7% versus 15.4% in arm A versus arm B, respectively; P <0.0001). Finally, amifostine appears to be protective against neurotoxicity (grade 3-4 neurotoxicity 3.7% versus 7.2%; P = 0.02). With a median follow-up of 24 months (range 2-41), time to progression was similar between the two groups. CONCLUSIONS: We showed that amifostine can exert some protection from the cumulative toxicity associated with this regimen. The results need to be confirmed in other randomized trials with this combination.
Subject(s)
Amifostine/pharmacology , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Ovarian Neoplasms/drug therapy , Radiation-Protective Agents/pharmacology , Adult , Aged , Carboplatin/administration & dosage , Carboplatin/adverse effects , Erythrocyte Count , Female , Humans , Infusions, Intravenous , Middle Aged , Mouth Mucosa/pathology , Neutropenia/chemically induced , Neutropenia/prevention & control , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Stomatitis/chemically induced , Stomatitis/prevention & control , Thrombocytopenia/chemically induced , Thrombocytopenia/prevention & controlABSTRACT
The aim of this study was to assess the long-term impact of high-dose chemotherapy (HDC) as consolidation in a large series (n = 55) of advanced chemosensitive ovarian cancer patients who were optimally cytoreduced at time of first surgery or at interval debulking surgery (IDS). HDC consisted of carboplatin (600 mg/m(2) days 1 and 2), etoposide (450 mg/m(2) days 1 and 2) and melphalan (50 mg/m(2), days 3 and 4). The primary endpoint of the study was the assessment of time to progression (TTP) and overall survival (OS). In September 2000 the overall population had a median follow-up of 55 months (range 17--137) and a TTP of 35 months with a 5-year TTP rate of 35% (CI 95%: 21--49) whereas OS averaged 75 months with a 5-year OS of 59% (CI 95%: 45--73). In patients achieving optimal primary cytoreduction the median TTP was 44 months with a 5-year rate of 43% (CI 95%: 26--60). In the same series the 5-year OS rate was 62% (CI 95%: 45--79) (median OS = 75 months). In patients who were optimally cytoreduced at the time of IDS the median TTP was 25 months and the 5-year TTP rate was 22% (CI 95%: 3--41) and median OS was 46 months with a 5-year OS rate of 50% (CI 95%: 27--73). HDC with hematopoietic support could represent an effective approach for the treatment of advanced optimally cytoreduced ovarian cancer patients with chemosensitive disease. Patients who underwent IDS because of unresectable tumors at the time of first surgery had the greater survival benefit from HDC.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Ovarian Neoplasms/drug therapy , Actuarial Analysis , Adult , Antineoplastic Combined Chemotherapy Protocols/toxicity , Carboplatin/administration & dosage , Carboplatin/toxicity , Disease-Free Survival , Dose-Response Relationship, Drug , Etoposide/administration & dosage , Etoposide/toxicity , Female , Humans , Longitudinal Studies , Melphalan/administration & dosage , Melphalan/toxicity , Middle Aged , Ovarian Neoplasms/mortality , Ovarian Neoplasms/surgery , Survival Rate , Treatment OutcomeABSTRACT
24 patients were enrolled into a phase I-II study conducted to determine the maximum tolerated doses of topotecan-gemcitabine in sequential combination and the response rate in platinum/paclitaxel resistant ovarian cancer patients. A total of 83 courses are evaluable, with a median number of three cycles administered per patients (range 2-7). Topotecan was administered on days 1-5 by 30 min i.v. infusion immediately after gemcitabine given by 30 min i.v. on days 1 and 3; cycles were repeated every 28 days. The starting doses were topotecan 0.7 mg/m(2) and gemcitabine 200 mg/m(2). Following dose levels were 08/400; 0.9/600; 0.9/800 for topotecan and gemcitabine, respectively. The maximum tolerated dose (MTD) was reached at dose level 3, the dose-limiting toxicity being represented by febrile neutropenia and thrombocytopenia. After the MTD was reached, granulocyte-colony-stimulating factor was administered in 27% of cycles. Mild and manageable was non hematological toxicity. All patients are so far evaluable for response. Among them 2 complete responses (8.3%; 95% CI: 2.6-19), 1 partial response (4.2%; 95% CI: 3.8-12), 9 no change (37.5%; 95% CI: 18-56.8) and 12 progressions (50%; 95% CI: 30-70) have been registered. Based on these data, there is no evidence that combining topotecan and gemcitabine is better than using either of the two drugs used separately.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Deoxycytidine/administration & dosage , Ovarian Neoplasms/drug therapy , Topotecan/administration & dosage , Adult , Aged , Antimetabolites, Antineoplastic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Blood Cell Count , Cisplatin/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Disease Progression , Drug Administration Schedule , Drug Resistance, Neoplasm , Enzyme Inhibitors/administration & dosage , Female , Humans , Middle Aged , Paclitaxel/administration & dosage , Recurrence , Topotecan/adverse effects , Treatment Outcome , GemcitabineABSTRACT
The treatment of recurrent or progressive ovarian cancer has limited therapeutic potential. The clinical outcome of second-line therapy largely depends on the potential chemo-sensitivity of the tumor expressed during up-front chemotherapy, as well as on the treatment-free interval from the last course of cytotoxic therapy. However, the identification of agents such as tamoxifen (TAM) at nontoxic doses, able to act synergistically with standard chemotherapy, may be useful to overcome resistance. Fifty patients with recurrent or progressive ovarian cancer following platinum (P)-based chemotherapy (28 platinum-resistant and 22 platinum-sensitive) entered a Phase II trial to evaluate the efficacy and toxicity of P re-challenge with the addition of TAM as a chemotherapy response modulator. The choice of the P compound (100 mg/m2 cisplatin or 400 mg/m2 carboplatin, q3 weeks) was made on the basis of the prior total cisplatin dose and the presence of neurotoxicity. TAM was administered at the doses of 80 mg/day for 30 days followed by 40 mg/day for the remaining period of treatment. Toxicity consisted mainly of mild to moderate nausea and vomiting (76%), peripheral neuropathy (43%), nephrotoxicity (4%), anemia (16%), leukopenia (58%) and thrombocytopenia (16%). The overall response to the P-TAM combination was 50% (complete response 30%; partial response 20%) with a median duration of 8.5 months (3-42). Sixty-four percent of the P-sensitive and 39% of the P-resistant patients responded (59% and 33%, respectively, for those bearing measurable disease). The overall median survival was 23 (3-48) and 19 months for the patients with measurable disease (20 months for the P-resistant group). This phase II trial confirmed the activity for a re-challenge employing a P compound and TAM in clinically defined P-resistant ovarian cancer patients. The mild toxicity profile and the relatively low cost of the treatment render further investigations on the P-TAM regimen worthwhile.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Ovarian Neoplasms/drug therapy , Adenocarcinoma, Clear Cell/drug therapy , Adenocarcinoma, Clear Cell/pathology , Adult , Aged , Aged, 80 and over , Carboplatin/administration & dosage , Carboplatin/adverse effects , Carcinoma, Endometrioid/drug therapy , Carcinoma, Endometrioid/pathology , Cisplatin/administration & dosage , Cisplatin/adverse effects , Cystadenocarcinoma, Serous/drug therapy , Cystadenocarcinoma, Serous/pathology , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Resistance, Neoplasm , Female , Humans , Middle Aged , Ovarian Neoplasms/pathology , Tamoxifen/administration & dosage , Tamoxifen/adverse effects , Treatment FailureABSTRACT
OBJECTIVE: We conducted a case-control study to analyze risk factors for ovarian cancer. METHODS: Cases included 440 women (age range 13-80 years, median 54) with a histologically confirmed diagnosis of epithelial ovarian cancer who were admitted to the Gynecological Oncological Department of Gynecologic Oncology at the Catholic University Hospital in Rome, Italy. Controls were women admitted to the same hospital where cases were identified for acute nongynecological, nonhormonal, and nonneoplastic conditions. A total of 868 control women (age range 19-80 years, median 55) were interviewed. RESULTS: In comparison with ever married women, the multivariate odds ratios (OR) of ovarian cancers was 2.0 (95% confidence interval, CI 1.3-3.2) for never married women. Cases and controls were similar as regards educational status and body mass index. No clear relation emerged between ovarian cancer and age at menarche, menopausal status, and age at menopause. In comparison with nulliparae, the estimated ORs were 0.8, 0.9, and 0.7, respectively, in women reporting one, two, or three births. Women reporting two or more induced abortions were at decreased risk of ovarian cancer (OR 0.5, 95% CI 0.3-1.0). In comparison with women reporting their first birth before 20 years of age, the multivariate ORs were 1.8, 2.0, and 2.8, respectively, for women reporting their first birth at age 20-24, 25-30, and >/=31 (chi(2) trend = 10.1). Breast-feeding for more than 1 year was associated with an OR of 0.5 (95% CI, 0.4-0.8). Forty-two (9.5%) cases and 164 (18.9%) controls reported ever oral contraceptive use: in comparison with never users, the multivariate OR was 0.4 (95% CI 0.3-0.6) for ever users, and the risk decreased with duration of use. The OR for ovarian cancer was 2.9 (95% CI, 1.5-5.8) for women with a family history of the disease. CONCLUSION: This study, conducted on a relatively low-risk population, confirms the role of oral contraceptive on ovarian cancer risk and the direct association with family history of ovarian cancer. It also indicates that a later age at first birth is directly, and induced abortion and breast-feeding are inversely, related to the risk of the disease.
Subject(s)
Ovarian Neoplasms/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Body Mass Index , Case-Control Studies , Education , Family Health , Female , Humans , Middle Aged , Parity , Risk Factors , Rome/epidemiology , Smoking , Socioeconomic FactorsABSTRACT
BACKGROUND: 5-Fluorouracil and cisplatin are characterized by in vitro synergism as well as radiosensitization. A phase I-II study was carried out on patients with invasive cervical carcinoma (FIGO IIB-IIIA) undergoing concomitant chemoradiation with 5-fluorouracil and cisplatin followed by radical surgery. METHODS: Twenty-six patients of 53 years median age, 24 with IIB tumor and 2 with IIIA tumor, all with squamous carcinoma, entered the study. The chemoradiation protocol included external radiotherapy to the pelvis: 39.6 Gy (180 cGy/daily); 5-fluorouracil: 1 g/m(2)/daily, in continuous intravenous infusion days 1-4 and 27-30; cisplatin: 20 mg/m(2)/daily days 1-4 and 27-30. Four weeks after the end of chemoradiotherapy, patients underwent restaging and then radical surgery with pelvic and lumboaortic lymphadenectomy. RESULTS: Twenty-six patients are evaluable for acute toxicity and 24 are evaluable for objective and pathologic response. Grade 3-4 thrombocytopenia or leukopenia was observed in 6 patients and grade 3 acute gastrointestinal toxicity in 3. After chemoradiation CR and PR were observed in 64 and 36% of cases, respectively (CR + PR = 100%). Two patients were excluded from surgery for other diseases. The remaining 24 patients were operated on; 23/24 patients showed negative section margins. The histology of the surgical specimen showed the absence of disease in 13 patients (54.2%), microscopic residual tumor in 4 patients (16.6%), residual disease =1 cm in 5 patients, and residual disease >1 cm in 2 patients. Median follow up was 33 months. Two-year actuarial local control was 91.7%. CONCLUSIONS: This study showed a particularly high rate of pathologic responses (complete + Tmic: 70.8%) and local control (2 years = 91.7%) in patients with advanced cervical cancer undergoing moderate doses of radiotherapy with concomitant chemotherapy followed by radical surgery.