ABSTRACT
BACKGROUND: Patients with recurrent/metastatic endometrial cancer that progresses after chemotherapy have limited treatment options and poor outcomes. Preclinical data suggest the oral mammalian target of rapamycin inhibitor everolimus may provide clinical benefit in these patients. METHODS: In this multicenter, open-label, phase 2 study, patients with advanced or metastatic endometrial cancer refractory to one or two previous chemotherapy regimens received everolimus 10 mg per day until progression or unacceptable toxicity. Primary end point was the non-progressive disease rate at 3 months. Secondary end points included duration of response, progression-free, and overall survival (OS), and safety. RESULTS: Forty-four patients were enrolled (median age, 65 years); 66% received one previous chemotherapy regimen. The 3-month non-progressive disease rate was 36% (95% confidence interval 22-52%), including two patients (5%) with partial response (PR). At 6 months, two additional patients experienced PR. Median duration of response was 3.1 months. Median progression-free and OS were 2.8 months and 8.1 months, respectively. The most common adverse events were anaemia (100%), fatigue (93%), hypercholesterolaemia (81%), and lymphopenia (81%). CONCLUSION: Everolimus demonstrated efficacy and acceptable tolerability in patients with chemotherapy-refractory advanced or metastatic endometrial cancer. These results support the further development of phosphatidylinositol 3-kinase-targeted therapies in endometrial cancer.
Subject(s)
Antineoplastic Agents/therapeutic use , Endometrial Neoplasms/drug therapy , Phosphoinositide-3 Kinase Inhibitors , Sirolimus/analogs & derivatives , TOR Serine-Threonine Kinases/antagonists & inhibitors , Aged , Antineoplastic Agents/adverse effects , Disease-Free Survival , Drug Resistance, Neoplasm , Everolimus , Female , Humans , Middle Aged , Sirolimus/adverse effects , Sirolimus/therapeutic use , Survival RateABSTRACT
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.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Carboplatin/administration & dosage , Female , Humans , Middle Aged , Neoplasm Recurrence, Local/mortality , Ovarian Neoplasms/mortality , Paclitaxel/administration & dosage , Survival Analysis , Topotecan/administration & dosageABSTRACT
PURPOSE: To define the recommended dose of the association of weekly irinotecan (Iri) and cisplatin (CP) with pelvic radiotherapy in Locally Advanced Cervical Cancer. PATIENTS AND METHODS: Stage IB2-IV cervix cancer patients were treated with escalating doses of Iri starting from 30 mg/m(2) and a fixed dose of CP at 20 mg/m(2), both weekly concomitantly with a 45-Gy pelvic irradiation. RESULTS: Fifteen patients entered the study, 6 at level 1 (Iri 30 mg/m(2)), 3 at level 2 (Iri 40 mg/m(2)) and 6 at intermediate dose (Iri 35 mg/m(2)). Median age was 47 years (34-72), FIGO stage IB (n=1), IIB (n=7), III (n=6), IVA (n=1). The recommended dose was weekly Iri 35 mg/m(2) and CP 20 mg/m(2). Dose limiting toxicities (grades 3-4) were diarrhea, abdominal pain, febrile neutropenia and fatigue. CONCLUSION: In cervix cancer patients, radiosensitization with weekly cisplatin and irinotecan is feasible, and the recommended doses are cisplatin 20 mg/m(2)/week and irinotecan 35 mg/m(2)/week for future phase II studies.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/radiotherapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Brachytherapy/adverse effects , Brachytherapy/methods , Camptothecin/administration & dosage , Camptothecin/adverse effects , Camptothecin/analogs & derivatives , Cisplatin/administration & dosage , Cisplatin/adverse effects , Combined Modality Therapy , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Humans , Irinotecan , Middle Aged , Neoplasm Staging , Radiotherapy/adverse effects , Radiotherapy/methods , Uterine Cervical Neoplasms/pathologyABSTRACT
Advanced ovarian carcinoma in early progression (<6 months) (AOCEP) is considered resistant to most cytotoxic drugs. Gemcitabine (GE) and oxaliplatin (OXA) have shown single-agent activity in relapsed ovarian cancer. Their combination was tested in patients with AOCEP in phase II study. Fifty patients pre-treated with platinum-taxane received q3w administration of OXA (100 mg m(-2), d1) and GE (1000 mg m(-2), d1, d8, 100-min infusion). Patient characteristics were a : median age 64 years (range 46-79),and 1 (84%) or 2 (16%) earlier lines of treatment. Haematological toxicity included grade 3-4 neutropaenia (33%), anaemia (8%), and thrombocytopaenia (19%). Febrile neutropaenia occurred in 3%. Non-haematological toxicity included grade 2-3 nausea or vomiting (34%), grade 3 fatigue (25%),and grade 2 alopecia (24%). Eighteen (37%) patients experienced response. Median progression-free (PF) and overall survivals (OS) were 4.6 and 11.4 months, respectively. The OXA-GE combination has high activity and acceptable toxicity in AOCEP patients. A comparison of the doublet OXA-GE with single-agent treatment is warranted.
Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols , Deoxycytidine/analogs & derivatives , Drug Resistance, Neoplasm , Organoplatinum Compounds/administration & dosage , Ovarian Neoplasms/drug therapy , Aged , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bridged-Ring Compounds/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Dose-Response Relationship, Drug , Female , Humans , Middle Aged , Organoplatinum Compounds/adverse effects , Oxaliplatin , Platinum/administration & dosage , Taxoids/administration & dosage , GemcitabineABSTRACT
BACKGROUND: This phase II study evaluated the clinical benefit of pegylated liposomal doxorubicin (PLD) and docetaxel (Taxotere) as first-line therapy for metastatic breast cancer (MBC). PATIENTS AND METHODS: MBC patients were enrolled to receive six cycles of PLD 35 mg/m2 (day 1) and docetaxel 40 mg/m2 (days 1 and 15), every 28 days (group A). Because of unacceptable toxic effects, doses were modified to PLD 30 mg/m2 (day 1) and docetaxel 75 mg/m2 (day 2), every 3 weeks (group B). The primary end point was clinical benefit. RESULTS: Sixty-seven patients were included (group A, 53; group B, 14). In both groups, the median number of cycles delivered was 4 and the overall dose intensity was 82% for docetaxel and 71% for PLD. In group A, main toxic effects were hematologic, palmar-plantar erythrodysesthesia (PPE), and stomatitis. In group B, higher rates of grade 3-4 PPE, febrile neutropenia, and hematologic toxic effects were reported. The rate of clinical benefit was 47%. Among patients with a measurable disease, 49% achieved a partial response, 27% had a stable disease, and 13% progressed, according to RECIST criteria. CONCLUSION: The combination of PLD and docetaxel delivered at planned doses in this study yields unacceptable toxicity and should not be used routinely in patients with MBC.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/pathology , Docetaxel , Doxorubicin/administration & dosage , Doxorubicin/analogs & derivatives , Female , Humans , Middle Aged , Neoplasm Metastasis , Polyethylene Glycols/administration & dosage , Taxoids/administration & dosageABSTRACT
OBJECTIVE: Cisplatin (Cp) plus topotecan (Tc) is the first combination chemotherapy to demonstrate a survival advantage over cisplatin alone in advanced cervical cancer. Combining Cp and Tc with an epidermal growth factor receptor (EGFR) inhibitor such as cetuximab (Ce) may increase the activity of chemotherapy. METHODS: Patients with advanced cervical squamous cell cancer or adenocarcinoma and at least one measurable target received intravenous Cp 50 mg/m(2) on day 1 plus Tc 0.75 mg/m(2)/day from days 1 to 3 every 3 weeks combined with Ce (initial dose of 400 mg/m(2) followed by subsequent weekly dose of 250 mg/m(2)). Objective response rate according to RECIST criteria was the primary end point; safety, progression free survival (PFS) and overall survival (OS) were secondary end points. RESULTS: Between April and July 2007, 19 out of the 44 planned patients were accrued before the study was stopped early due to excessive toxicity. The most frequent adverse event was severe myelosuppression with grades 3-4 neutropenia (72%), grades 3-4 thrombocytopenia (61%), and grade 3 anemia (44.5%). The main grades 3-4 non-hematologic toxicities were infection (39%) and febrile neutropenia (28%), skin reactions (22%), renal toxicity (11%), and pulmonary embolism (11%). Five (28%) patients died during the treatment including 3 deaths related to treatment toxicity. Six (32%) evaluable patients achieved a partial response. The median times of PFS and OS were 172 and 220 days, respectively. CONCLUSION: In this phase II trial, the combination Cp-Tc-Ce induced a high rate of serious adverse and/or fatal events at standard dose and schedule. Cetuximab plus platinum-based combination chemotherapy should be further explored with caution in the future in advanced cervix cancer.
Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Uterine Cervical Neoplasms/drug therapy , Adult , Aged , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cetuximab , Cisplatin/administration & dosage , Cisplatin/adverse effects , Disease-Free Survival , Drug Synergism , Female , Humans , Middle Aged , Topotecan/administration & dosage , Topotecan/adverse effectsABSTRACT
The clinical activity and toxicity of the triple combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), cyclophosphamide, and cisplatin was assessed in both previously treated and untreated women with advanced ovarian carcinoma. Paclitaxel 175 mg/m2 was administered over 3 hours following standard premedication (prednisolone, dexchlorpheniramine, and cimetidine). Cisplatin 80 mg/m2 and cyclophosphamide 600 mg/m2 were given 6 to 12 hours after paclitaxel. Treatment was given at 3-week intervals for six cycles. Twenty-seven patients entered the study; 23 were evaluable for toxicity and 17 for response. Paclitaxel appeared to add additional efficacy to the standard cisplatin/cyclophosphamide regimen. Both the overall and complete remission rates were very high (88% and 70%, respectively), and histologically confirmed complete remissions exceeded 60%. Longer follow-up is needed to determine the duration of these responses. The primary toxicities included leukoneutropenia, peripheral neuropathy, asthenia, and alopecia. Only two of 23 patients withdrew because of toxicity, however, and only two treatment cycles were complicated by neutropenic fever requiring intravenous antibiotics. No life-threatening toxicities were encountered, although the peripheral neuropathy was poorly and slowly reversible and may have a significant impact on the patients' quality of life.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Ovarian Neoplasms/drug therapy , Paclitaxel/administration & dosage , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/administration & dosage , Cyclophosphamide/administration & dosage , Feasibility Studies , Female , Humans , Middle Aged , Neoplasm Staging , Ovarian Neoplasms/pathology , Remission InductionABSTRACT
In this phase I/II study, we assessed the impact of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in the treatment of advanced ovarian carcinoma combined with the standard regimen cisplatin/cyclophosphamide given as follows: paclitaxel 175 mg/m2 (over 3 hours perfusion with standard premedication), cisplatin 80 mg/m2 (6 to 12 hours after paclitaxel), and cyclophosphamide 400 mg/m2. From February 1994 to January 1996, 27 patients (median age, 55 years; age range, 35 to 74 years) were entered into the study. Eight patients had distant metastases and 19 had early locoregional disease (stage III, 18 patients; stage IC, one patient). Twenty-two patients had undergone prior surgery (simple biopsy, six patients; optimally debulked, nine patients; suboptimally debulked, seven patients). Twenty-one patients had received no prior chemotherapy and six were previously treated with at least one platinum-based regimen. A maximum of six courses of paclitaxel/cisplatin/cyclophosphamide were given every 21 days. Twenty-three patients were evaluable for toxicity: neutropenia (World Health Organization grade 3/4), 91% of patients; thrombopenia (World Health Organization grade 3/4), 13% of patients; two episodes of neutropenia with fever; and neurotoxicity grade 3, 17% of patients. Alopecia grade 3 was reported in all patients. No hypersensitivity reactions and no cardiac toxicity was observed. Among 17 patients evaluable for response (patients with stage IV disease or stage III suboptimally debulked), 12 (70%) clinical complete responses (CRs) and three (18%) partial responses were observed. Among the 12 patients with CRs, 10 underwent second-look laparotomy and seven of them (70%) achieved a pathologic CR. In the group of 11 chemotherapy-naive patients evaluable for response, eight (72%) achieved a CR and three (28%) achieved a partial response. This combination seems to be safe, with very acceptable toxicity, and also seems to be highly active in the treatment of patients with advanced ovarian carcinoma.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Ovarian Neoplasms/drug therapy , Adult , Aged , Cisplatin/administration & dosage , Cyclophosphamide/administration & dosage , Drug Administration Schedule , Female , Humans , Middle Aged , Paclitaxel/administration & dosageABSTRACT
The French Groupe des Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO) conducted a multicenter phase II study of carboplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to evaluate the efficacy and side effects of this combination in pretreated advanced ovarian cancer. Patients with progressive ovarian carcinoma during or after platinum-based chemotherapy received paclitaxel 175 mg/m2 intravenously over 3 hours followed by intravenous carboplatin over 30 minutes every 4 weeks. The dose of carboplatin was calculated using a projected area under the concentration-time curve of 5 mg/mL x min. Of the 50 patients entered, 50 were evaluable for toxicity and 42 for response. There were eight complete and 10 partial responses, for an overall response rate of 43% (95% confidence interval, 28% to 56%). Overall response rates in platinum refractory patients and in those with early (> or = 3 and < 12 months) and late (> or = 12 months) relapse was 28%, 33%, and 71%, respectively. Median response duration, progression-free survival, and overall survivals were 8, 6, and 14 months, respectively. The most frequent and severe toxicity was myelosuppression. Grades 3 and 4 neutropenia occurred in 30% and 23% of cycles, and granulocyte colony-stimulating factor was administered in 6%. Only one case of neutropenic fever was observed. Grades 3 and 4 thrombocytopenia occurred in 3% and 1% of cycles, respectively. Alopecia and moderate nausea or vomiting were frequent. Transitory peripheral neuropathy was present in 45% of patients but was severe in only one patient. One early death was observed due to progressive disease and possibly to therapy. The combination of paclitaxel 175 mg/m2 as a 3-hour infusion and carboplatin dosed to an area under the concentration-time curve of 5 is an effective therapy in patients previously treated with platinum-based chemotherapy and may be administered safely to outpatients who relapse after one or two lines of chemotherapy.
Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/administration & dosage , Carcinoma/drug therapy , Ovarian Neoplasms/drug therapy , Paclitaxel/administration & dosage , Adolescent , Adult , Aged , Alopecia/chemically induced , Antineoplastic Agents/adverse effects , Antineoplastic Agents, Phytogenic/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Area Under Curve , Carboplatin/adverse effects , Carcinoma/pathology , Cisplatin/administration & dosage , Confidence Intervals , Disease Progression , Female , France , Granulocyte Colony-Stimulating Factor/therapeutic use , Humans , Injections, Intravenous , Middle Aged , Nausea/chemically induced , Neoplasm Recurrence, Local/drug therapy , Neoplasm Staging , Neutropenia/chemically induced , Ovarian Neoplasms/pathology , Paclitaxel/adverse effects , Peripheral Nervous System Diseases/chemically induced , Remission Induction , Safety , Survival Rate , Thrombocytopenia/chemically induced , Treatment OutcomeABSTRACT
Five cases of calcification of the breast due to filariasis in Congolese women are reported. The cases were discovered during mammographies carried out for suspect carcinoma (4 cases) and benign tumor (1 case). The geographic origin of the patients, a past history of subconjunctival filarial migration in 2 individuals, the bilateral localization, and, above all, the radiographic appearance and size of the calcifications, suggested that the images were due to Loa loa.
Subject(s)
Breast Diseases/etiology , Calcinosis/etiology , Filariasis/complications , Loiasis/complications , Adult , Aged , Animals , Congo , Female , Humans , Mammography , Middle AgedABSTRACT
Fotemustine and dacarbazine constitute the most active single chemotherapeutic agents in the treatment of melanoma. In this phase II study we evaluated the activity and toxicity of a combination of fotemustine, dacarbazine and vindesine as a means of increasing response rate and survival time. Between September 1989 and November 1993, 43 patients with advanced melanoma were treated with a combination of 100 mg/m2 fotemustine on days 1 and 8, 250 mg/m2 dacarbazine on days 15 and 16 and 2 mg/m2 vindesine on days 15 and 16 as induction treatment. After a 5-week rest period, the patients exhibiting a response or stable disease received the same drugs administered once every 28 days as maintenance therapy until either progression or toxicity was observed. Among 41 evaluable patients, there were six complete responses and eight partial responses. The overall response rate was 32% (95% confidence interval: 18-46%), with 8 months median duration of response. Median survival time was 10 months. This regimen was well tolerated. From this large phase II study, we conclude that such a combination is active against advanced malignant melanoma and seems to be more effective than fotemustine or dacarbazine used alone, especially on visceral metastatic sites.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Melanoma/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bone Marrow Diseases/chemically induced , Combined Modality Therapy , Dacarbazine/administration & dosage , Dacarbazine/adverse effects , Disease-Free Survival , Female , Follow-Up Studies , Humans , Male , Melanoma/mortality , Melanoma/pathology , Melanoma/surgery , Middle Aged , Neoplasm Metastasis , Nitrosourea Compounds/administration & dosage , Nitrosourea Compounds/adverse effects , Organophosphorus Compounds/administration & dosage , Organophosphorus Compounds/adverse effects , Remission Induction , Risk , Salvage Therapy , Survival Rate , Treatment Outcome , Vindesine/administration & dosage , Vindesine/adverse effectsABSTRACT
Endometrial carcinoma is one of the most common gynaecological cancers in Western countries. About 75% of the patients present limited disease, confined to the uterus that can be cured by surgery. However, one third of the patients will need systemic treatment because of metastatic or relapsing disease. Hormonotherapy response rates are less than 20%. In monochemotherapy, the higher response rates are constantly observed with doxorubicin or cisplatinum (25-35%). Most commonly used combination are CAP (cyclophosphamide, doxorubicin, cisplatinum) or AP (doxorubicin, cisplatinum), giving 35 to 60% of objective responses. Recent results of large randomized trials have demonstrated marginal, if any, effect of cyclophosphamide and superiority of doxorubicin-cisplatinum combination compared to doxorubicin alone for response and survival. Chemotherapy as hormonotherapy remains palliative. Median response duration is 4 to 6 months and median overall survival duration is 7 to 10 months. Currently, hormonotherapy-chemotherapy combination have not been proved to be more effective than chemotherapy alone.
Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Agents/therapeutic use , Endometrial Neoplasms/drug therapy , Progesterone Congeners/therapeutic use , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cisplatin/administration & dosage , Combined Modality Therapy , Doxorubicin/administration & dosage , Drug Resistance, Neoplasm , Endometrial Neoplasms/pathology , Endometrial Neoplasms/surgery , Female , Humans , Middle Aged , Neoplasm Metastasis , Phosphoramide Mustards/administration & dosage , Prognosis , Survival AnalysisABSTRACT
BACKGROUND: Metastatic breast cancer chemotherapy in the elderly is considered effective in carefully selected patients, but there is little data regarding its effect in vulnerable patients. METHODS: We evaluated tumour response (primary endpoint), feasibility and outcomes after six courses of an adapted dose of pegylated liposomal doxorubicin (PLD) (40 mg/m(2) every 28 days) as first-line chemotherapy for hormone-resistant MBC. RESULTS: Of 60 patients >70 years (median 77 years), 15% had performance status ≥2 and 73% had visceral metastases. Geriatric assessment included: ≥2 comorbidities, 42%; ≥1 deficiency in Activities of Daily Living (ADL), 10% and Instrumental ADL (IADL), 82%; living in residential homes, 12%; albumin <35 g/L, 17%; body mass index (BMI) <21, 20%; depression, 17%; and lymphocytes ≤1 × 10(3)/mm(3), 27%. Complete response, partial response and stable disease were observed in 5%, 15% and 60%, respectively, but only 48% completed six cycles. Treatment discontinuations were mostly due to disease progression (18%) and non-haematological (NH) toxicities (22%). Eight patients died during treatment (three possibly related to PLD), and 15 had unplanned hospital admissions. Exploratory analyses to identify geriatric covariates associated with treatment outcomes revealed severe haematological toxicities significantly correlated with lymphocytes ≤1 × 10(3)/mm(3). NH toxicities correlated with age ≥80 years and living in residential homes. Progression-free survival (median 6.1 months) decreased with age, deficiency in IADL, cardiac dysfunction and living in residential homes. Overall survival (median 15.7 months) also decreased with living in residential homes. CONCLUSION: Despite manageable haematological toxicities and expected response rates, PLD feasibility was poor in unselected elderly patients.
Subject(s)
Antibiotics, Antineoplastic/therapeutic use , Breast Neoplasms/drug therapy , Doxorubicin/analogs & derivatives , Polyethylene Glycols/therapeutic use , Activities of Daily Living , Age Factors , Aged , Aged, 80 and over , Antibiotics, Antineoplastic/administration & dosage , Antibiotics, Antineoplastic/adverse effects , Breast Neoplasms/mortality , Breast Neoplasms/secondary , Disease-Free Survival , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Doxorubicin/therapeutic use , Drug Administration Schedule , Female , France , Geriatric Assessment , Heart Diseases/complications , Homes for the Aged , Humans , Kaplan-Meier Estimate , Multivariate Analysis , Nursing Homes , Odds Ratio , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/adverse effects , Proportional Hazards Models , Risk Assessment , Risk Factors , Surveys and Questionnaires , Time Factors , Treatment OutcomeSubject(s)
Adenocarcinoma/epidemiology , Breast Neoplasms/epidemiology , Congo/epidemiology , Female , Humans , MaleSubject(s)
HIV Infections/complications , Neoplasms/complications , Adult , Aged , Congo/epidemiology , Female , Humans , Male , Middle Aged , Neoplasms/epidemiologyABSTRACT
The objective of the study is to determine whether surgery influences the outcome of stage IV ovarian cancer. The study design is as follows: From May 1995 to December 2000, 129 patients with FIGO stage IV ovarian cancer, recruited in 42 centers, were prospectively included in GINECO first-line randomized studies of platinum-based regimens with paclitaxel administered simultaneously or sequentially. In all, 109 were eligible for this study. Standard peritoneal cytoreductive surgery was defined as a procedure including at least total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and peritoneal debulking. Surgery was considered optimal if residual lesions were smaller than 1 cm. The Kaplan-Meier method was used to compare survival. Initial abdominopelvic cytoreductive surgery was considered standard in 55 (54%) patients. Abdominopelvic surgery was optimal in 29 patients and nonoptimal in 26. Twenty-two (22%) patients had a simple biopsy, and 25 (24%) patients underwent substandard surgery. Twenty-two of these 47 patients without initial standard surgery underwent a second surgical procedure, and 17 of the 22 patients completed standard surgery. The median overall survival time in the entire population was 24.3 months (95% confidence interval [CI], 19.5-29.1 months). Patients treated without a cytoreductive surgical procedure had significantly worse median survival (15.1 months; 95% CI, 5.4-24.9 months) than patients who had optimal primary surgery (22.9 months; 95% CI, 15.6-30.1 months), nonoptimal primary surgery (27.1 months; 95% CI, 21.2-32.9 months), or neoadjuvant chemotherapy followed by surgery (45.5 months; 95% CI, 23.5-67.5 months) (P= .001). In conclusion, this study shows a significant benefit of debulking surgery in stage IV ovarian cancer patients who responded to neoadjuvant chemotherapy. Neoadjuvant chemotherapy can help to select patients for surgery.
Subject(s)
Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/surgery , Adult , Aged , Disease Progression , Disease-Free Survival , Epithelial Cells/pathology , Female , Humans , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Ovarian Neoplasms/pathology , Retrospective StudiesABSTRACT
BACKGROUND: Platinum-based chemotherapy is standard second-line treatment of patients with advanced ovarian cancer (AOC) in late relapse. Pegylated liposomal doxorubicin (PLD) has significant single-agent activity in this setting. Therefore, we evaluated the use of PLD plus carboplatin in this patient population. PATIENTS AND METHODS: PLD 30 mg/m(2) followed by carboplatin at area under the curve (AUC) 5 mg.min/ml, repeated every 28 days for a maximum of nine cycles, was administered to 104 women with AOC relapsing >or=6 months after completion of first- or second-line therapy with platinum-taxane-based regimens. RESULTS: Overall response was 63%, with a 38% complete response, median progression-free survival of 9.4 months, and median overall survival (OS) of 32 months. Grade 3 or 4 neutropenia occurred in 51% of patients, but febrile neutropenia in only 3%. Nonhematologic toxic effects were primarily grades 1 and 2, with low rates of alopecia and neurotoxicity. CONCLUSIONS: PLD plus carboplatin is highly effective, prolongs OS, and is well tolerated in women with AOC in late relapse previously treated with both platinum and taxanes. Evaluation of this regimen in phase III trials is warranted.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Endometrioid/drug therapy , Cystadenocarcinoma, Serous/drug therapy , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/drug therapy , Adult , Aged , Carboplatin/administration & dosage , Doxorubicin/administration & dosage , Doxorubicin/analogs & derivatives , Female , France , Humans , Middle Aged , Neoplasm Staging , Ovarian Neoplasms/pathology , Polyethylene Glycols/administration & dosage , Remission Induction , Safety , Salvage Therapy , Survival Rate , Treatment OutcomeABSTRACT
ICON3 trial results have suggested that CAP and carboplatin-taxol regimens as first-line treatment of advanced ovarian cancer (AOC) yield similar survival. We explored the impact of increased dose of cyclophosphamide in a modified CAP regimen on the disease-free survival (DFS) and overall survival (OS) of AOC patients. From February 1994 to June 1997, 164 patients were randomised to receive six cycles every 3 weeks of either standard CEP (S) combining cyclophosphamide (C), 500 mg m(-2), epirubicin (E) 50 mg m(-2), and cisplatin (P) 75 mg m(-2) or intensive CEP (I) with E and P at the same doses, but with (C) 1800 mg m(-2) and filgrastim 5 mug kg(-1) per day x 10 days. Response was evaluated at second-look surgery. Patient characteristics were well balanced. Except for grade 3-4 neutropaenia (S: 54%, I: 38% of cycles), Arm1 presented a significantly more important toxicity: infection requiring antibiotics, grade 3-4 thrombocytopaenia, anaemia, nausea-vomiting, diarrhoea, mucositis. Median follow-up was 84 months. DFS (15.9 vs 14.8 months) and OS (33 vs 30 months) were not significantly different between S and I (P>0.05). Increasing cyclophosphamide dose by more than 3 times with filgrastim support in the modified CAP regimen CEP induces more toxicity but not better efficacy in AOC.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Ovarian Neoplasms/drug therapy , Adolescent , Adult , Aged , Carboplatin/administration & dosage , Carcinoma, Endometrioid/drug therapy , Cisplatin/administration & dosage , Cyclophosphamide/administration & dosage , Cystadenocarcinoma, Serous/drug therapy , Disease-Free Survival , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Granulocyte Colony-Stimulating Factor/administration & dosage , Humans , Middle Aged , Treatment OutcomeABSTRACT
Thirty-three patients, with histologically proven advanced nonsmall cell lung cancer (NSCLC) were treated at Institut Curie with a three-drug combination chemotherapy. The regimen consisted of cisplatin 25 mg/m2 per day continuous infusion (CI) and 5-fluorouracil (5-FU) CI 600 mg/m2 on 5 consecutive days with 30 minutes infusion navelbine 25 mg/m2 on days 1 and 5 only. Cycles were repeated every 28 days. Response was evaluated after three cycles. One patient died of an ischemic cerebrovascular stroke after the third cycle. Thirty-two pts were evaluable. Partial response was achieved in 11/20 patients with stage III disease (55%) and in 7/12 patients with stage IV disease (58%). WHO grade 4 toxicities were leucopenia 31%, thrombocytopenia 4%, and mucositis 4%. The tolerance was acceptable. Median survival was 19 months for stage III and 9.5 months for stage IV. We conclude that the combination of 5-FU, navelbine, and cisplatin is an effective chemotherapy regimen for patients with advanced stage NSCLC.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adult , Aged , Cisplatin/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Infusions, Parenteral , Male , Middle Aged , Vinblastine/administration & dosage , Vinblastine/analogs & derivatives , VinorelbineABSTRACT
In 42 months, 175 patients (171 women and 4 men) were followed for mammary tumor in the Department of Medicine and Cancerology of l'Hopital General of Brazzaville. Among them, 63 files were retained for the study, corresponding to women under the age of 30. The study of these cases enabled the authors to establish the relatively important frequency of large tumors (larger than 5 cm), and the similarity of the general aspects of the pathology of mammary tumors, as compared to european studies.