Phase 2 trial of single-agent gemcitabine in platinum-paclitaxel refractory ovarian cancer

OBJECTIVE: There is a need to find agents with activity in platinum and taxane refractory ovarian cancer to be employed as second-line therapy in the malignancy. Limited clinical trial experience has suggested that gemcitabine possesses activity in this clinical setting. We wished to further define the level of activity of gemcitabine in women with well-characterized platinum/taxane refractory disease. METHODS: Patients with ovarian or fallopian tube cancer or primary carcinoma of the peritoneum, whose disease had either failed to respond to a platinum and taxane treatment, or had responded but the "treatment free interval (TFI)" was < or =3 months, or if the TFI was >3 months and they had been retreated with the agents and not responded (or experienced a TFI of <3 months), were eligible for treatment on this phase 2 single institution protocol. Gemcitabine was administered weekly (as a 1-h infusion) for 3 weeks, followed by 1-week break. RESULTS: A total of 51 patients were treated on this trial. The initial dose level (1250 mg/m(2)/week) resulted in excessive toxicity (fatigue, fever/chills, bone marrow suppression). The modified starting dose (1000 mg/m(2)/week) resulted in a more acceptable side effect profile. Eight patients (16%) with measurable disease (n = 4) or evaluable disease by CA-125 criteria (n = 4) achieved an objective response (median duration of response: 4 months; range 2-13 months). CONCLUSION: Single agent gemcitabine possesses modest, but definite, activity in patients with well-characterized platinum/taxane resistant ovarian cancer. It is reasonable to consider this drug for second-line (or later) treatment in this clinical setting.     

Gemcitabine in the treatment of ovarian cancer

Abstract. Hansen SW. Gemcitabine in the treatment of ovarian cancer.
Gemcitabine is a nucleoside antimetabolite with established activity against several solid tumors. The activity of the drug in patients with ovarian cancer has been reviewed both in patients who have received single drug treatment and in patients who have received combination chemotherapy. The response rates, with single agent gemcitabine, range from 13 to 24% both in previously treated and untreated patients. Doublets consisting of gemcitabine-cisplatin or gemcitabine-paclitaxel, in previously treated patients, induced response in 53% and 40% of the patients, respectively. In three studies, first-line treatment with the combination of cisplatin and gemcitabine induced remission in 53% to 71% of the patients. The triplet, including gemcitabine, paclitaxel, and cisplatin or carboplatin, has been examined in previously treated patients and a response rate of 100% was observed. In previously untreated patients the combination of gemcitabine, paclitaxel, and carboplatin has been preferred due to a more favorable toxicity profile. The activity of this combination, observed in 25 evaluable patients, was very high as all patients responded. Complete remission was observed in 60% of the patients and partial remission in 40%. Based on these promising data the triplet consisting of gemcitabine, paclitaxel, and carboplatin has been included in randomized trials both in the US and in Europe.     

Review of gemcitabine-based combinations for platinum-resistant ovarian cancer

Abstract.   Sehouli J. Review of gemcitabine-based combinations for platinum-resistant ovarian cancer. Int J Gynecol Cancer 2005; 15(Suppl. 1): 23–30.
Gemcitabine, an analog of deoxycytidine, is an anticancer nucleoside with proven activity in different solid malignancies. The efficacy of gemcitabine as a single agent or as part of a combination treatment has been evaluated in several trials, and antitumor activity has been observed in patients with sensitivity and resistance to both platinum and paclitaxel. In this context, preclinical studies have shown that gemcitabine-based combinations increase the cytotoxic action of the treatment and can potentially overcome drug resistance. The toxicity profile of gemcitabine, and its proven action in relapsed ovarian cancer, allows for the development of a hypothesis stating that a specific choice of drugs with different mechanisms and non–cross-resistance can increase the chance of response and prolong its duration and that of other outcome measures. This article provides an update of new clinical approaches with gemcitabine in combination with other nonplatinum drugs for the management of patients with platinum-resistant ovarian cancer.     

PARP inhibitors in ovarian cancer: Current status and future promise

Clinical investigation of poly(ADP-ribose) polymerase (PARP) inhibitors for ovarian cancer treatment has rapidly evolved from observations of single-agent in vitro activity of these agents in BRCA-deficient cancer cells in 2005 to the initiation of multiple phase III studies in 2013. With clinical trial design and treatment of ovarian cancer increasingly based on histological and molecular characteristics, PARP inhibitors are on the horizon of becoming the first biologic agents to be used to treat ovarian cancer based upon pre-selection characteristics of the patient's cancer. PARP inhibitors are most active in ovarian cancers that have defects or aberrations in DNA repair; use of these agents has been of particular interest in high grade serous cancers (HGSC), where studies have shown that ~ 50% of HGSC have abnormalities of DNA repair through BRCA germline and somatic mutation, post-translational changes of BRCA, and abnormalities of other DNA repair molecules. In addition, as aberrant DNA pathways in other histological subtypes of ovarian cancer are identified, and through the combination of PARP inhibitors with other biologic agents, the pool of eligible patients who may benefit from PARP inhibitors will likely expand. Pending review by the Food and Drug Administration (FDA) and the outcome of confirmatory phase III studies, PARP inhibitors could become the first FDA-approved biologic agent for ovarian cancer and also the first new FDA-approval in ovarian cancer since carboplatin and gemcitabine were approved for platinum sensitive ovarian cancer in 2006. This review discusses the PARP inhibitors that are currently in testing for ovarian cancer treatment and the future of this class of anti-cancer agents.     

Gemcitabine reverses cisplatin resistance: demonstration of activity in platinum- and multidrug-resistant ovarian and peritoneal carcinoma

OBJECTIVE: Preclinical models in an ovarian cancer cell line (A2780) demonstrate synergistic activity with the combination of gemcitabine and cisplatin compared to either single agent alone. Platinum resistance is related to expression of excision repair proteins, one of which (ERCC-1) has been identified as playing a critical role in the synergy of gemcitabine and cisplatin. We evaluated the cisplatin and gemcitabine regimen in patients with platinum refractory and multidrug refractory ovarian and peritoneal carcinoma. METHODS: Gemcitabine (750 mg/m(2)) was administered intravenously over 30 min followed by cisplatin (30 mg/m(2)) on Days 1 and 8 every 21 days. Day 8 therapy was canceled for an absolute neutrophil count <1000/mm(3) or platelet count <75,000/mm(3). Sequential dose reductions of gemcitabine to 600, 400, and 300 mg/m(2) were prescribed in the event of canceled therapy, neutropenic sepsis, or severe thrombocytopenia (platelets <20,000/m(3)). RESULTS: Thirty-six platinum- and paclitaxel-resistant patients were studied. Thirty-five were evaluable for response, of which 6 had progressed on gemcitabine as a single agent. Fifteen of the patients responded (42.9%, 95% CI 28.0-59.1%). Eleven were partial clinical responses and 4 were complete clinical responses, with 4 of the 6 patients who had failed gemcitabine as a single agent responding. Among the responding patients the median response duration was 11 months (range 4-14 months). For all patients the progression-free interval was 6 months (range 1-14 months). The median survival was 12 months. CONCLUSION: The combination of gemcitabine and cisplatin is active in patients who are platinum resistant. Additionally, activity is demonstrated even in patients who have previously been resistant to gemcitabine.     

Three cases of hemolytic uremic syndrome in ovarian cancer patients treated with combination gemcitabine and pegylated liposomal doxorubicin

BACKGROUND: Hemolytic uremic syndrome (HUS) is a rare coagulation disorder characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute uremia. Reports have described this fatal syndrome in association with cytotoxic agents. To our knowledge, no case reports of HUS in ovarian cancer patients receiving treatment with combination gemcitabine and pegylated liposomal doxorubicin (PLD) have been reported. CASE REPORTS: Three patients with recurrent ovarian carcinoma each developed profound hypertension and peripheral edema while receiving combination gemcitabine and PLD. The first patient had rapid hemolysis, thrombocytopenia, renal failure and respiratory distress. The other patients experienced slowly progressive renal failure and mild hematologic abnormalities. Two of the three patients had favorable outcomes. CONCLUSION: The reported incidence of gemcitabine-induced HUS is rare. Clinicians should suspect HUS if blood pressure elevation or peripheral edema develop.     

New cytotoxics and non-cytotoxics in epithelial ovarian cancer

Abstract. Eisenhauer EA. New cytotoxics and non-cyto-toxics in epithelial ovarian cancer.
Several new cytotoxic agents with activity in relapsed ovarian cancer are being combined with paclitaxel plus platinum as the first step to assess their impact in randomized trials against the standard treatment. These include topotecan, gemcitabine, epirubicin, and liposomal doxorubicin. Because of overlapping toxicities, there have been challenges in combining some of these agents in full dose with combination paclitaxel plus platinum. These have been overcome by use of sequenced administration. In addition to these new agents, novel non-cytotoxic drugs targeting specific signaling molecules or the tumor microenvironment provide additional avenues for clinical investigation. Many of these agents are rational to assess in ovarian cancer where laboratory research has pinpointed a number of alterations in molecules involved in cell signaling and cell cycle control. Examples include the antibody to HER 2/neu, agents targeting protein kinase C alpha, the p53 gene, and matrix metalloproteinase inhibitors. The challenges facing their assessment include how to determine adequate dosing when toxic effects are minimal and how to assess evidence of antitumor activity, short of conducting randomized studies. Finally, how best to use such agents together with conventional chemotherapy, in combination or in sequence, is unknown. Large clinical studies with some of these agents will provide some answers to their impact and how best to use them in the first-line management of advanced epithelial ovarian cancer.     

Preclinical in vivo activity of a combination gemcitabine/liposomal doxorubicin against cisplatin-resistant human ovarian cancer (A2780/CDDP)

Both gemcitabine and liposomal doxorubicin are antineoplastic drugs with clinical activity in platinum-refractory ovarian cancer. The purpose of this study was to evaluate the antitumor activity of a combination gemcitabine/liposomal doxorubicin administered to athymic mice bearing cisplatin-resistant human ovarian cancer (A2780/CDDP) xenografts. Emphasis was on the use of very low doses of each drug and of different dosing schedules. Data obtained showed that combined treatment with 80 mg/kg gemcitabine and 15 mg/kg liposomal doxorubicin produced a significant enhancement of antitumor activity compared with monotherapy at the same doses of these agents. Noteworthy is the fact that the majority of xenograft-bearing animals receiving the combination therapy demonstrated a complete tumor regression at the end of the study. A similar trend was observed when doses of both drugs were reduced to 20 mg/kg gemcitabine and to 6 mg/kg liposomal doxorubicin. Again, three out of ten mice receiving the combination were tumor free at the end of the study. No significant differences were observed in antitumor activity when comparing the simultaneous vs the consecutive dosing schedule. Remarkably, no additive toxicity was observed in any experimental trials. These data encourage clinical trials to prove the advantages of this combination treatment with respect to the single-agent chemotherapy in platinum-refractory ovarian cancer patients.     

Response of combination platinum and gemcitabine chemotherapy for recurrent epithelial ovarian carcinoma

OBJECTIVE: It has been postulated that gemcitabine inhibits DNA repair, and platinum resistance is due to increased DNA repair activity. The addition of gemcitabine to platinum-based agents may have synergistic tumoricidal activity. METHODS: Retrospective chart review of all patients with recurrent, persistent, or progressive fallopian tube or ovarian carcinoma treated with a platinum-based compound and gemcitabine from 2001 to present was performed. RESULTS: Twenty-nine patients on second to eight line chemotherapy met inclusion criteria. The median age was 53 years. Twenty-two patients received cisplatin and gemcitabine, and 7 patients received carboplatin and gemcitabine based on results of chemoresistance assays or prior chemorelated toxicities. The intent to treat was with six cycles of gemcitabine (1000 mg/m(2)) and either cisplatin (75 mg/m(2)) or carboplatin (AUC 5) day 1 and gemcitabine only on day 8 of a 21-day cycle. The median number of cycles administered was six. There were 20 grade 3 and 4 toxicities and 63% of patients by cycle 6 needed erythropoietin marrow support and 19% needed GCSF support by cycle 4. Twenty-one patients required discontinuation of day 8 that most commonly occurred at cycle 4. Eleven (38%) had CR, 5 (17%) had PR, 6 (21%) had SD, and 7 (24%) had PD, which is a 55% overall response. Nineteen of 29 patients (66%) showed platinum resistance to initial therapy. Of those, four (21%) had CR, four (21%) had PR, six (32%) had SD, and five (26%) with PD, which demonstrates a 42% overall response rate for this particular subset of patients. CONCLUSIONS: Adjuvant combination platinum-based agent with gemcitabine is a very effective and well-tolerated treatment for recurrent fallopian tube or ovarian carcinoma; even in those who exhibit initial platinum resistance.     

Gemcitabine-induced radiation recall dermatitis following whole pelvic radiation therapy

OBJECTIVES: Radiation recall dermatitis secondary to gemcitabine use has been reported in isolated cases of patients treated for breast and lung cancers. There have been no reports of radiation recall dermatitis from gemcitabine after whole pelvic radiation therapy employed as a treatment of a gynecologic cancer. CASE: A 67-year-old woman was treated with whole pelvic radiation for palliation of lower extremity swelling and pain due to recurrent ovarian adenocarcinoma. Three months later, the patient was treated with gemcitabine for three courses. Therapy was discontinued secondary to severe cellulitis and edema of the skin of the anterior abdominal wall in the field of her prior radiation therapy. CONCLUSIONS: Radiation recall dermatitis secondary to gemcitabine should be considered in any patient with pelvic or lower abdominal skin abnormalities after pelvic radiation and subsequent gemcitabine therapy.     

Efficacy of gemcitabine in heavily pretreated advanced ovarian cancer patients

Single agent gemcitabine was used in recurrent epithelial ovarian cancer patients after standard treatment with debulking surgery and platin-paclitaxel based chemotherapy. Response rates and toxicity results were evaluated retrospectively. Gemcitabine was given in 1000 mg/m2 intravenous infusion over 30 minutes at 1, 8, 15 days of every 28 days. Clinical response was evaluated with clinical findings, serum CA 125 levels, and computerized tomography. Twenty-two patients--ten as second-line, 11 as third-line, and one as fourth line--received gemcitabine. Seven patients received six courses, nine cases three, five cases two and one case one course of treatment. There were four (18.2%) partial and two (9.1%) complete responses with an overall response rate of 27.3%. Stable disease was also observed in three more cases. The progression-free interval was found to be a median of three months. Grade 3-4 neutropenia was seen in two (9.1%) and grade 3-4 thrombocytopenia was seen in four (18.2%) cases. Pancytopenia was observed in one (4.5%) patient. There was no grade 3-4 non-hematological toxicity. Antitumoral activity is encouraging in heavily pretreated ovarian cancer patients. A short progression-free interval is noticeable in responding cases. Toxicity is mainly hematologic and moderate.     

Ovarian protection with gonadotropin-releasing hormone agonists during cyclophosphamide therapy in systemic lupus erythematosus

Administration of cyclophosphamide (CYC), an alkylating agent used to treat malignancies and severe rheumatic diseases, creates a risk of ovarian insufficiency that is related to the intensity and duration of therapy and the age of the patient. To preserve reproductive capacity in the appropriate clinical setting, oocyte, embryo, and/or ovarian tissue cryopreservation are recommended. Medical protection with depot gonadotropin-releasing hormone agonists (GNRHa) has emerged as a potential means to preserve both fertility and ovarian function through the suppression of ovarian activity during treatment with alkylators. We review the trials of GNRHa for ovarian protection in both cancer and rheumatic disease patients. Trials in cancer patients receiving CYC alone, or in combination with other gonadotoxic agents that have employed several different GNRHa have yielded mixed results. Trials in lupus patients receiving lower doses of CYC alone utilizing depot leuprolide acetate have tended to show favorable results.     

Therapeutic advances in ovarian cancer.

The propensity of ovarian cancer to recur--even after initial chemotherapeutic responses--is a problem that has been given a great deal of attention during the past year in the literature dealing with the treatment of ovarian cancer. Most of the articles address techniques to improve the percent of initial and secondary treatment responses. Several studies have described cytoreductive techniques to decrease the remaining tumor size for improved chemotherapeutic response. Cross-resistance between platinum analogues has been reconfirmed. However, improved secondary responses were seen when repeat treatment with platinum agents were preceded by a longer interval from initial platinum agent therapy. Radiation therapy has been shown to offer little solution to recurrent disease except possibly in a select group of patients with microscopic disease at second-look laparotomy. Reports on the use of carboplatin continue to demonstrate good initial responses, with decreased toxicity compared with cisplatin. Granisetron has been shown to significantly decrease the nausea and vomiting caused by emetogenic chemotherapy like cisplatin.     

Long-term disease-free survival effected by gemcitabine in a heavily pretreated patient with recurrent ovarian carcinoma

Introduction Gemcitabine has been shown to have modest activity and low and well-tolerated toxicity in heavily pretreated patients with recurrent ovarian carcinoma.Case report A 46-year-old patient with recurrent ovarian carcinoma who failed with two previous lines of chemotherapy has for the last 40 months received third-line chemotherapy with gemcitabine. This has resulted in an extraordinary long-term disease-free survival of 38 months. Toxicity has been low and well tolerated.Conclusion Gemcitabine seems to be an attractive agent for salvage chemotherapy in ovarian carcinoma patients who failed with prior lines of chemotherapy.     

Differential in vitro effects of chemotherapeutic agents on primary cultures of human ovarian carcinoma

The treatment of ovarian cancer principally relies on the use of platinum and taxane chemotherapeutic agents. Short-term clinical results have been encouraging, but long-term responses remain limited. In this report, an in vitro assay system that utilizes cells grown from human tumor explants has been used to quantitatively evaluate responses to relevant concentrations of alternative chemotherapeutic agents. The results suggest that there are significant differences in the responses of explant-derived cultured cells to the different agents tested. In an evaluation of 276 primary ovarian cancer specimens, five nonstandard drugs were tested in 51 cases. Of these 51 cases, cyclophosphamide had the highest rate of response at 67%, followed by doxorubicin at 61%, gemcitabine at 49%, etoposide at 48%, and topotecan at 14%. Venn diagrams, representing the in vitro responses to the platins and taxanes, as well as the responses to the nonstandard drugs, illustrate that there clearly are distinct differences among patients in a given population. These data underscore the potential importance of evaluating each patient's response to a number of different drugs to optimize the therapeutic decision-making process.     

Fertility preservation in oncology

Survival rates of childhood and pre-pubertal female cancer patients are constantly increasing. However the lifesaving treatments carry a significant risk for infertility. Chemotherapy and radiotherapy might induce oocyte and follicular loss, infertility and premature ovarian failure. In order to preserve the fertility potential, several options are currently available, many of those should be considered as experimental. Ovarian transposition out of the radiation field may considerably reduce the radiation dose and should be considered for patients younger than 40 years of age. The benefits of GnRH analog are not clear yet and apoptosis inhibiting agents are not available. Embryo cryopreservation is a well established technique and should be offered to patients with spouses; when the patient does not have a male partner, oocyte cryopreservation or vitrification can be performed. When the cancer treatment cannot be delayed for ovarian stimulation or the tumor is hormone sensitive then collection of immature oocytes from unstimulated ovaries is particularly useful. The oocytes are matured in-vitro and either fertilized and cryopreserved as embryos or vitrified as mature oocytes. Ovarian tissue cryopreservation has the potential of preserving thousands of primordial follicles. The thawed ovarian tissue can be autotransplented orthotopically or heterotopically. Until now, only one human live birth has been reported and critical issues like the potential risk of transplanting malignant cells and the survival of the grafts have to be addressed. The strategy for preservation of fertility prior to cancer treatment should be tailored according to the patients age, presence of a partner, type of malignant disease, therapeutic agent, and time interval available. The patient should obviously be informed that some of the methods are still experimental.     

Pharma Update Genitalkarzinome

Ovarian cancer

In early stage ovarian cancer chemotherapy containing platinum is recommended. In an advanced or recurrent situation combined chemotherapy with carboplatin/paclitaxel (area under the curve AUC5 175 mg/m²) is indicated. The vascular endothelial growth factor (VEGF) targeting agent bevacizumab can prolong the progress-free interval. For the treatment of platinum-sensitive ovarian cancer the preferred agents are carboplatin/gemcitabine, carboplatin/paclitaxel and carboplatin/caelyx. Platinum-resistant recrudescence primarily indicates a monochemotherapy and the recommended therapeutic options are polyethylene glycol (PEG) liposomal doxorubicin/topotecan/gemcitabine/paclitaxel.

Cervical cancer

A combined radiochemotherapy containing cisplatin is considered to be the standard of care in neoadjuvant and adjuvant treatment as well as in recurrent situations. Neoadjuvant dose-dense chemotherapy improves the 5-year survival rate and reduces overall mortality. Adjuvant chemotherapy only is not indicated. In a recurrent or metastasized situation for radiation-naive patients radiochemotherapy is indicated. The only approved regimen in Germany is a combination of cisplatin and topotecan. Results of the GOG 240 trial confirmed an enhancement of the progress-free survival with addition of the antibody bevacizumab.

Endometrial cancer

Of all endometrial cancer patients 20?% are considered to be high risk patients. The recurrence rate is 50?%. According to the current German S2K guidelines in all patients presenting with a TNM stage Ib G3, II and III as well as all serous or small cell endometrial carcinomas, platinum chemotherapy with carboplatin/paclitaxel (AUC5 175 mg/m²) is indicated sequential to radiation. In the palliative situation local surgical treatment or radiation is the main option. A possible combination with either gestagens or cytostatic therapy depends on the hormone receptor status.

Vulvar cancer

Radiochemotherapy is indicated in inoperable situations, extensive recrudescence or in non-in sano resected patients. In metastasized patients the use of a combined chemotherapy is criticized due to the high toxicity and low response rate.     

Remarks and conclusions on ovarian cancer treatment

Abstract. Poveda A. Remarks and conclusions on ovarian cancer treatment.
Ovarian cancer is still the fourth cause of death by cancer among women and the most fatal among gynecological tumors. The purpose of this symposium has been to report and discuss the new developments in the treatment of patients with ovarian cancer, the majority of whom still present with advanced disease. It also tries to make clear to the participants what is evidence-based and what is not. Although the main topic of the symposium is advanced disease, this edition included some updated information on the treatment of early disease under the heading "is early disease really early"; the importance of screening and molecular approaches are highlighted. In addition studies reported in the literature on the role of chemotherapy versus no chemotherapy in high-risk patients with early ovarian cancer have been updated.
The pace of new agent development has increased, and it would be helpful to have more efficient preclinical models and early phase-clinical trials to guide the selection of active agents for phase III evaluation. Reaching international consensus is a challenge, but offers the opportunity to test multiple regimens more efficiently against a single control population, rather than conducting multiple smaller studies with redundant internal controls. If indeed answers to the relevant questions are to be obtained more quickly, then a network of current national or international groups could potentially facilitate this.     

Phase II trial of weekly paclitaxel (80 mg/m2) in platinum and paclitaxel-resistant ovarian and primary peritoneal cancers: a Gynecologic Oncology Group study

OBJECTIVE: To evaluate the activity of single agent weekly paclitaxel in patients with both platinum and paclitaxel (delivered every 3 weeks)-resistant ovarian cancer. METHODS: Forty-eight patients with platinum and paclitaxel-resistant ovarian cancer (defined as progression during, or recurrence < 6 months following, their prior treatment with both agents) received single agent weekly paclitaxel (80 mg/m2/week) until disease progression (assuming acceptable toxicity). Following the initial 12 weekly doses, treatment could be given for 3 weeks, with a 1 week break. RESULTS: In this chemoresistant population, the objective response rate was 20.9%. Serious adverse events were relatively uncommon (neuropathy-grade 2: 21%; grade 3: 4%; and grade 3 fatigue: 8%). CONCLUSION: The weekly administration of paclitaxel can be a useful management approach in women with both platinum and paclitaxel (given every 3 weeks)-resistant ovarian cancer. It would be appropriate to directly compare weekly to every 3-week paclitaxel delivery in the setting of primary chemotherapy of advanced ovarian cancer.     

A phase II study of gemcitabine plus carboplatin in platinum-sensitive, recurrent ovarian carcinoma

OBJECTIVES: Gemcitabine and carboplatin each have demonstrated effectiveness without increased neurotoxicity in pretreated patients with ovarian cancer. We evaluated the efficacy and safety of gemcitabine plus carboplatin in patients with recurrent ovarian cancer in a multicenter phase II study. METHODS: Women with histologically proven measurable or evaluable epithelial ovarian cancer (any FIGO) who relapsed > or =6 months after discontinuation of first-line, platinum-containing therapy received gemcitabine 1000 mg/m(2) on days 1 and 8 and carboplatin AUC 4 on day 1 (after gemcitabine) every 21 days for up to six cycles. RESULTS: Of the 40 enrolled/evaluable patients, 6 (15%) had complete response and 19 (47.5%) had partial response (PR), including one patient with PR in nonmeasurable disease (PRNM), for an overall response rate of 62.5% (95% CI, 45.8-77.3%). The median duration of response was 7.8 months (95% CI, 6.7-10.0), the median time to progressive disease was 9.6 months (95% CI, 8.5-11.0), and the median time to treatment failure was 9.3 months (95% CI, 8.2-10.4). The main grade 3/4 toxicities were neutropenia (78% of patients), leukopenia (30%), thrombocytopenia (18%), and anemia (15%); no grade 4 nonhematologic toxicities occurred, and grade 3 nonhematologic toxicities were mild. CONCLUSIONS: The combination of gemcitabine and carboplatin is active and feasible in platinum-sensitive patients with recurrent ovarian cancer. This regimen is undergoing further evaluation in a large phase III trial.