Ovarian cancer treatment: what is new

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 is, year after year, 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 it clear to the participants what is evidence-based and what is not. Mature data of both classic studies like GOG-111, OV-10, and more recent studies like GOG-158, AGO-OVAR-3, and the intergroup paclitaxel/epirubicin/carboplatin (TEC) versus paclitaxel/carboplatin (TC) study have been presented. Other current controversial issues included in this edition were sequential single-agent versus simultaneous administration of combination chemotherapy, the role of combination chemotherapy in second-line treatment, the role of consolidation therapy, the role of anthracyclines in the treatment, and cost-effectiviness studies in ovarian cancer. Although the main topic of the symposium is advanced disease, this edition included the results of two parallel randomized studies (ACTION and ICON1) on the treatment of early disease. In addition, new trends in early detection of 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.

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Randomized Phase III Trial of Gemcitabine Compared With Pegylated Liposomal Doxorubicin in Patients With Platinum-Resistant Ovarian Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.09.6735 ◽

2007 ◽

Vol 25 (19) ◽

pp. 2811-2818 ◽

Cited By ~ 243

Author(s):

David G. Mutch ◽

Mauro Orlando ◽

Tiana Goss ◽

Michael G. Teneriello ◽

Alan N. Gordon ◽

...

Keyword(s):

Ovarian Cancer ◽

Liposomal Doxorubicin ◽

Single Agent ◽

Pegylated Liposomal Doxorubicin ◽

Progression Free Survival ◽

Therapeutic Index ◽

Phase Iii ◽

End Points ◽

Platinum Resistant ◽

Significant Difference

Purpose Ovarian cancer (OC) patients experiencing progressive disease (PD) within 6 months of platinum-based therapy in the primary setting are considered platinum resistant (Pt-R). Currently, pegylated liposomal doxorubicin (PLD) is a standard of care for treatment of recurrent Pt-R disease. On the basis of promising phase II results, gemcitabine was compared with PLD for efficacy and safety in taxane-pretreated Pt-R OC patients. Patients and Methods Patients (n = 195) with Pt-R OC were randomly assigned to either gemcitabine 1,000 mg/m2 (days 1 and 8; every 21 days) or PLD 50 mg/m2 (day 1; every 28 days) until PD or undue toxicity. Optional cross-over therapy was allowed at PD or at withdrawal because of toxicity. Primary end point was progression-free survival (PFS). Additional end points included tumor response, time to treatment failure, survival, and quality of life. Results In the gemcitabine and PLD groups, median PFS was 3.6 v 3.1 months; median overall survival was 12.7 v 13.5 months; overall response rate (ORR) was 6.1% v 8.3%; and in the subset of patients with measurable disease, ORR was 9.2% v 11.7%, respectively. None of the efficacy end points showed a statistically significant difference between treatment groups. The PLD group experienced significantly more hand-foot syndrome and mucositis; the gemcitabine group experienced significantly more constipation, nausea/vomiting, fatigue, and neutropenia but not febrile neutropenia. Conclusion Although this was not designed as an equivalency study, gemcitabine and PLD seem to have a comparable therapeutic index in this population of Pt-R taxane-pretreated OC patients. Single-agent gemcitabine may be an acceptable alternative to PLD for patients with Pt-R OC.

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Phase III Study of Pirarubicin / Cyclophosphamide / CDDP(CTP) vs. Doxorubicin / Cyclophosphamide / CDDP(CAP) Combination Chemotherapy in Advanced Epithelial Ovarian Cancer

Korean Journal of Gynecologic Oncology and Colposcopy ◽

10.3802/kjgoc.1999.10.2.148 ◽

1999 ◽

Vol 10 (2) ◽

pp. 148

Author(s):

Yong Beom Kim ◽

Jae Weon Kim ◽

Noh Hyun Park ◽

Yong Sang Song ◽

Soon Beom Kang ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Combination Chemotherapy ◽

Phase Iii ◽

Phase Iii Study ◽

Advanced Epithelial Ovarian Cancer

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Long-term follow-up of a phase III intergroup study of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study.

Journal of Clinical Oncology ◽

10.1200/jco.1997.15.7.2564 ◽

1997 ◽

Vol 15 (7) ◽

pp. 2564-2569 ◽

Cited By ~ 374

Author(s):

S B Saxman ◽

K J Propert ◽

L H Einhorn ◽

E D Crawford ◽

I Tannock ◽

...

Keyword(s):

Urothelial Carcinoma ◽

Combination Chemotherapy ◽

Performance Status ◽

Single Agent ◽

Phase Iii ◽

Long Term Follow Up ◽

Intergroup Trial ◽

Advanced Urothelial Carcinoma

PURPOSE A previously reported randomized intergroup trial demonstrated that combination chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) was superior to single-agent cisplatin in patients with advanced urothelial carcinoma. We conducted a long-term analysis of patients included in the intergroup trial to examine factors associated with long-term survival. PATIENTS AND METHODS Two-hundred fifty-five assessable patients with urothelial carcinoma were randomized to receive either single-agent cisplatin (70 mg/m2 on day 1) or combination chemotherapy with methotrexate (30 mg/m2 on days 1, 15, and 22), vinblastine (3 mg/m2 on days 2, 15, and 22), doxorubicin (30 mg/m2 on day 2), and cisplatin (70 mg/m2 on day 2). Courses were repeated every 28 days. The association between patient characteristics and survival was assessed using Cox proportional hazards models. RESULTS With long-term follow-up evaluation, survival in the M-VAC arm continues to be superior to cisplatin (P = .00015, log-rank test). Predictors of survival include performance status, histology, and the presence of liver or bone metastasis. Only 3.7% of the patients randomized to M-VAC are alive and continuously disease-free at 6 years. CONCLUSION Long-term follow-up evaluation of the intergroup trial confirms that M-VAC is superior to single-agent cisplatin in patients with advanced urothelial carcinoma; however, durable progression-free survival is rare. Patients with non-transitional-cell histology, poor performance status, and/or bone or visceral involvement fare poorly and are unlikely to benefit significantly from M-VAC chemotherapy.

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Single agent vs. combination chemotherapy for ovarian cancer

American Journal of Clinical Oncology ◽

10.1097/00000421-198502000-00042 ◽

1985 ◽

Vol 8 (1) ◽

pp. 33-38 ◽

Cited By ~ 5

Author(s):

Gregorio Delgado ◽

Frederick P. Smith ◽

Ellen K. McLaughlin ◽

Nancy Tuholski

Keyword(s):

Ovarian Cancer ◽

Combination Chemotherapy ◽

Single Agent

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ACELARATE: A phase III, open label, multicentre randomised clinical study comparing Acelarin (NUC-1031) with gemcitabine in patients with metastatic pancreatic carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.tps537 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. TPS537-TPS537 ◽

Cited By ~ 3

Author(s):

Daniel H. Palmer ◽

Paul J. Ross ◽

Paul Silcocks ◽

William Greenhalf ◽

Olusola Olusesan Faluyi ◽

...

Keyword(s):

Pancreatic Adenocarcinoma ◽

Combination Chemotherapy ◽

Performance Status ◽

Single Agent ◽

Active Agent ◽

Phase Iii ◽

Secondary Outcome ◽

Open Label ◽

Metastatic Pancreatic Adenocarcinoma ◽

Phase Iii Study

TPS537 Background: Single agent gemcitabine still remains an appropriate choice for patients with metastatic pancreatic adenocarcinoma who are not suitable for combination therapy. Known resistance factors, such as low hENT1 and dCK, and CDA overexpression limit gemcitabine’s efficacy. NUC-1031 (Acelarin), is designed to overcome this resistance and deliver significantly higher intracellular levels of the active agent, dFdCTP, than gemcitabine. In Phase I studies Acelarin has shown activity in a range of metastatic cancers, including pancreatic, biliary and ovarian cancers. This Phase III study is designed to show superiority of Acelarin over gemcitabine in patients unsuitable for combination chemotherapy. Methods: To date, 85 patients have been randomised in this multicentre, Phase III study comparing Acelarin with gemcitabine first-line in patients with metastatic pancreatic adenocarcinoma. Patients must have a Performance Status of 0-2 and be unsuitable for combination chemotherapy. To detect a hazard ratio of 0.705 between the two arms, 270 events must be obtained from 328 patients, assuming a median survival of 6 months in the control arm. Currently, pts are being recruited at 27 centres. Patients receive either 825mg/m2 Acelarin or 1000mg/m2 gemcitabine on Day 1, 8 and 15 of a 28-day cycle until disease progression. The primary outcome measure is Overall Survival. Secondary outcome measures include Progression Free Survival, Response Rate, Disease Control Rate and Toxicity. Translational research will explore the use of biomarkers for predictive benefit of Acelarin over gemcitabine. Clinical trial information: ISRCTN16765355.

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The role of neoadjuvant chemotherapy in elderly patients with borderline or locally advanced pancreatic cancer: Is it safe and feasible?

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.685 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 685-685 ◽

Cited By ~ 1

Author(s):

Atsushi Oba ◽

Christopher Hanyoung Lieu ◽

Cheryl Lauren Meguid ◽

Sarah Lindsey Davis ◽

Alexis Diane Leal ◽

...

Keyword(s):

Pancreatic Cancer ◽

Elderly Patients ◽

Combination Chemotherapy ◽

Single Agent ◽

Locally Advanced ◽

Neoadjuvant Treatment ◽

Advanced Pancreatic Cancer ◽

Survival Advantage ◽

Locally Advanced Pancreatic Cancer

685 Background: For borderline resectable (BRPC) or locally advanced pancreatic cancer (LAPC), neoadjuvant (NAT) FOLFIRINOX or gemcitabine plus nab-paclitaxel (GnP) are standard treatment options and these regimens have shown a survival advantage over single-agent gemcitabine. However, the role of these modern therapeutic regimens in elderly patients is debatable. In this analysis, we evaluated the outcomes of neoadjuvant treatment (NAT) with combination chemotherapy in elderly patients. Methods: 230 consecutive patients who underwent neoadjuvant treatment for BRPC/LAPC discussed and planned for NAT at the University of Colorado Cancer Center from January 2011 to March 2019 were reviewed. 214 patients who received FOLFIRINOX (n = 143) or GnP (n = 71) were eligible for analysis. We divided all patients into three groups ( < 70, 70-74, ≥75 years) and compared the short-term and long-term outcomes. Results: Of 214 patients, patients < 70 (n = 147) received FOLFIRINOX more frequently than the other groups (p < 0.001): FOLFIRINOX: 115 cases, GnP: 32 cases, 70-74 years (n = 33): FOLFIRINOX: 15 cases, GnP: 18 cases, and ≥75 years (n = 34): FOLFIRINOX: 13 cases, GnP: 21 cases. Resection rates were not statistically different between three groups ( < 70: 62%, 70-74: 70%, ≥75 years: 56%, p = 0.504). There was a slight trend towards worse survival in the two older groups (Median Survival Time [MST]: < 70: 23.2 mo., 70-74: 19.5 mo., ≥75 years: 17.6 mo., p = 0.075) The FOLFIRINOX group was superior to GnP group in all three groups (MST: < 70: 25.6 vs 18.2 mo., p = 0.017; 70-74: 33.2 vs 16.1mo., p = 0.029; ≥75 years: not reached vs 16.1 mo., p = 0.135). There were no toxic deaths or 30 day mortality after pancreatectomy in the study population. Conclusions: Neoadjuvant combination chemotherapy regimens were safe and feasible for elderly patients. Neoadjuvant therapy with FOLFIRINOX was associated with a survival advantage vs GnP and is an good option for fit and elderly patients ≥75 years.

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Clinical Trials in Recurrent Ovarian Cancer

International Journal of Gynecological Cancer ◽

10.1097/igc.0b013e31821bb8aa ◽

2011 ◽

Vol 21 (4) ◽

pp. 771-775 ◽

Cited By ~ 112

Author(s):

Michael Friedlander ◽

Edward Trimble ◽

Anna Tinker ◽

David Alberts ◽

Elisabeth Avall-Lundqvist ◽

...

Keyword(s):

Ovarian Cancer ◽

Clinical Trials ◽

Gynecologic Cancer ◽

Recurrent Ovarian Cancer ◽

Consensus Conference ◽

Ca 125 ◽

Therapeutic Approaches ◽

Cooperative Research ◽

International Consensus

The 4th Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup was held in Vancouver, Canada, in June 2010. Representatives of 23 cooperative research groups studying gynecologic cancers gathered to establish international consensus on issues critical to the conduct of large randomized trials. Group C, 1 of the 3 discussion groups, examined recurrent ovarian cancer, and we report the consensus reached regarding 4 questions. These included the following: (1) What is the role of cytoreductive surgery for recurrent ovarian cancer? (2) How do we define distinct patient populations in need of specific therapeutic approaches? (3) Should end points for trials with recurrent disease vary from those of first-line trials? (4) Is CA-125 progression alone sufficient for entry/eligibility into clinical trials?

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Impact of Young Age on Treatment Efficacy and Safety in Advanced Colorectal Cancer: A Pooled Analysis of Patients From Nine First-Line Phase III Chemotherapy Trials

Journal of Clinical Oncology ◽

10.1200/jco.2010.33.5281 ◽

2011 ◽

Vol 29 (20) ◽

pp. 2781-2786 ◽

Cited By ~ 26

Author(s):

Charles D. Blanke ◽

Brian M. Bot ◽

David M. Thomas ◽

Archie Bleyer ◽

Claus-Henning Kohne ◽

...

Keyword(s):

Colorectal Cancer ◽

Combination Chemotherapy ◽

Older Patients ◽

Advanced Colorectal Cancer ◽

Single Agent ◽

Young Patients ◽

Progression Free Survival ◽

Young Age ◽

Phase Iii ◽

Grade 3

Purpose Colorectal cancer predominantly occurs in the elderly, but approximately 5% of patients are 50 years old or younger. We sought to determine whether young age is prognostic, or whether it influences efficacy/toxicity of chemotherapy, in patients with advanced disease. Methods We analyzed individual data on 6,284 patients from nine phase III trials of advanced colorectal cancer (aCRC) that used fluorouracil-based single-agent and combination chemotherapy. End points included progression-free survival (PFS), overall survival (OS), response rate (RR), and grade 3 or worse adverse events. Stratified Cox and adjusted logistic-regression models were used to test for age effects and age-treatment interactions. Results A total of 793 patients (13%) were younger than 50 years old; 188 of these patients (3% of total patients) were younger than 40 years old. Grade 3 or worse nausea (10% v 7%; P = .01) was more common, and severe diarrhea (11% v 14%; P = .001) and neutropenia (23% v 26%; P < .001) were less common in young (younger than 50 years) than in older (older than 50 years) patients. Age was prognostic for PFS, with poorer outcomes occurring in those younger than 50 years (median, 6.0 v 7.5 months; hazard ratio, 1.10; P = .02), but it did not affect RR or OS. In the subset of monotherapy versus combination chemotherapy trials, the relative benefits of multiagent chemotherapy were similar for young and older patients. Results were comparable when utilizing an age cut point of 40 years. Conclusion Young age is modestly associated with poorer PFS but not OS or RR in treated patients with aCRC, and young patients have more nausea but less diarrhea and neutropenia with chemotherapy in general. Young versus older patients derive the same benefits from combination chemotherapy. Absent results of a clinical trial, standard combination chemotherapy approaches are appropriate for young patients with aCRC.

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Immunologic Approaches to Ovarian Cancer Treatment

Journal of Clinical Oncology ◽

10.1200/jco.2007.11.0775 ◽

2007 ◽

Vol 25 (20) ◽

pp. 2884-2893 ◽

Cited By ~ 36

Author(s):

Paul Sabbatini ◽

Kunle Odunsi

Keyword(s):

Ovarian Cancer ◽

Immune Surveillance ◽

Chemotherapy Resistance ◽

Optimal Strategies ◽

Tumor Infiltrating Lymphocytes ◽

Tumor Rejection ◽

Phase Iii ◽

Minimal Disease ◽

Infiltrating Lymphocytes

The clinical course of ovarian cancer is often marked by periods of relapse and remission until chemotherapy resistance develops. Patients in remission with minimal disease burdens are ideally suited for the evaluation of immune-based strategies. The role of immune surveillance in improving outcome has been supported by the correlation of increased survival with the presence or absence of tumor-infiltrating lymphocytes in a given patient. Major obstacles to the development of successful immune strategies include the identification of tumor-restricted immunogenic targets, generation of a sufficient immune response to cause tumor rejection, and approaches to overcome evasion of immune attack. As optimal strategies are being developed, many questions remain. Some of the questions are as follows: What is the best antigen form (eg, peptides, proteins, or tumor lysates)? What are the appropriate adjuvants? Are monovalent or multivalent vaccines likely to be more effective? What is the optimal frequency and duration of vaccination? How should antigen-specific responses be monitored? How should the anticancer response be maintained? In this review, we will explore representative examples of immune strategies under investigation for patients with ovarian carcinoma that illustrate many of these issues. We will review ongoing phase III studies for patients in first clinical remission. Basic principles generic to all these immunotherapeutic approaches will be discussed in the hopes of yielding the most promising results as the field continues to evolve.

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