Role For Gemcitabine As Second-line Chemotherapy in Recurrent Clear Cell Ovarian Cancer

In a recent 2014 retrospective analysis involving 72 recurrent ovarian clear cell patients who underwent second-line therapy at one of 20 Italian centers over a 16-year period, the researchers noted that a small subgroup of patients who received the drug gemcitabine (Gemzar®) appeared to have a higher rate of tumor response, as compared to women who were treated with topotecan (Hycamtin®) or pegylated liposomal doxorubicin (Doxil®).

Clear Cell Carcinoma of the Ovary

In the July 2014 issue of Oncology, Italian researchers present an interesting retrospective analysis of patients with recurrent clear-cell ovarian cancer [1], a fairly chemoresistant subtype of ovarian cancer that can be difficult to treat.

This retrospective analysis included 72 recurrent ovarian clear cell patients (OCCC), who underwent second-line therapy at one of 20 Italian centers over a 16-year period (as part of the “Multicenter Italian Trial in Ovarian Cancer” or “MITO-9”).

In 56% of the OCCC patients, the clear cell histology was “pure,” meaning the predominant cell type identified within the primary tumor was classified as clear cell (i.e., a subtype of epithelial ovarian cancer) by a molecular pathologist. Twenty-five patients were platinum-resistant, 18 patients were platinum-sensitive with a platinum-free interval (PFI) of 6-to-12 months, and 29 patients had a PFI >12 months. Upon disease recurrence, 47% of patients were treated with platinum chemotherapy (e.g., carboplatin or cisplatin) based upon PFI.

The overall tumor response rate (RR) to the use of platinum drugs was 80%, with 55%, 100%, and 80% RRs in patients with PFIs of 6-to-12 months, >12 months, and >24 months, respectively. The RR to non-platinum drugs in resistant OCCC patients was 33%. Among the non-platinum drugs used in primary and secondary resistant cases, gemcitabine (Gemzar®), administered to 12 OCCC patients, produced higher anti-cancer activity (RR = 66%), as compared to topotecan (Hycamtin®) or liposomal doxorubicin (Doxil®) (number of patients = 31; RRs = 33% and 10%, respectively).

The Italian researchers concluded that the overall study results suggest that the treatment of recurrent OCCC, in general, should be based upon the duration of the patient’s PFI, as is customary in the treatment of other epithelial ovarian cancer subtypes. However, the data relating to the platinum-resistant OCCC patients evaluated in the Italian study suggest that gemcitabine (Gemzar®) was the drug that produced the greatest anti-cancer activity.

Notably, the results reported by the Italian researchers are consistent with the similar findings reported in a small number of previous studies involving an equally small number of recurrent OCCC patients. [2 – 5]

Also appearing in the July 2014 Oncology issue is a commentary written by Maurie Markman, M.D., the President of the Medicine and Science unit of the Cancer Treatment Centers of America (CTCA).[6] Dr. Markman oversees the CTCA national clinical team, with a focus on the application of all clinical and translational research to patient care. In his commentary, Dr. Markman notes the importance of retrospective studies as a “long-established tradition in clinical cancer investigation.” Dr. Markman highlights the potential inportance of retrospective studies as noted below.

• Single institutional data or large multicenter efforts examining past experiences can serve both as “hypothesis-generating” elements for a future prospective clinical study, an idea to be explored in a translational laboratory research project, and even as confirmation of the results of a reported study in a more heterogeneous patient population.

• Retrospective analyses can provide critically relevant data in populations known to be poorly represented in cancer clinical trials and may identify adverse events potentially not recognized in the often highly homogenous groups of study participants.

• The safety and the efficacy associated with longer observation periods and a more prolonged therapy than reported in many prospective clinical trials can be revealed through retrospective examinations of previously treated patients.

Within this context, Dr. Markman addresses the limitations of the Italian recurrent OCCC retrospective analyses cited above, but he also emphasizes the potential benefit of that study, as follows:

“Of course, it must be emphasized that the very limited sample size does not permit any definitive conclusions regarding the relative utility of any individual strategy, including providing a truly meaningful ‘objective response rate’. However, recognizing the rarity of this specific malignant condition (72 total [OCCC] patients identified in a period of 16 years at 20 centers), this retrospective experience will likely be of some value to individual oncologists needing to consider potential therapeutic options for a patient with recurrent clear-cell ovarian cancer. Further, in the event a multi-institutional prospective trial is ultimately undertaken in this most uncommon clinical setting, the results of this retrospective analysis should surely help to inform the planned study design.” [emphasis added]

At Libby’s H*O*P*E*, we generally recommend that recurrent OCCC patients speak to their doctor about the potential benefits (and limitations) associated with (i) molecular/genomic tumor profiling,  and (ii) chemosensistivity and resistance assay (CSRA) testing. The use of both forms of tumor testing may provide a recurrent OCCC patient and her doctor(s) with additional insights related to specific treatment options. In the event that neither form of tumor testing is possible, the results from the Italian study discussed above suggest that the use of gemcitabine (Gemzar®) to treat recurrent OCCC should be, at a minimum, considered by a recurrent OCCC patient and her doctor.

In addition, we strongly recommend that a newly-diagnosed or recurrent OCCC patient should consider the drugs being currently evaluated, as of this writing, in open OCCC patient-dedicated clinical trials, including as temsirolimus (Torisel®) [7], sunitinib (Sutent®) [8], ENMD-2076 [9], and dasatinib (Sprycel®) [10].

References:

1./ Esposito F et al. Second-line chemotherapy in recurrent clear cell ovarian cancer: Results from the Multicenter Italian Trials in Ovarian Cancer (MITO-9). Oncology 2014;86:351-358. PubMed PMID:24942520.

2./ Yoshino K, et al. Salvage chemotherapy for recurrent or persistent clear cell carcinoma of the ovary: a single-institution experience for a series of 20 patients. Int J Clin Oncol. 2013 Feb;18(1):148-53. doi: 10.1007/s10147-011-0357-5. Epub 2011 Dec 10. PubMed PMID: 22160560.

3./ Komiyama S et al. A heavily pretreated patient with recurrent clear cell adenocarcinoma of the ovary in whom carcinomatous peritonitis was controlled successfully by salvage therapy with gemcitabine. Arch Gynecol Obstet. 2008 Dec;278(6):565-8. Epub 2007 Jun 19. Erratum in: Arch Gynecol Obstet. 2009 Feb;279(2):271. Komiyama, Shin [corrected to Komiyama, Shin-ichi]. PubMed PMID: 17576588.

4./ Ferrandina G et al. A case of drug resistant clear cell ovarian cancer showing responsiveness to gemcitabine at first administration and at re-challenge. Cancer Chemother Pharmacol. 2007 Aug;60(3):459-61. Epub 2007 Apr 11. PubMed PMID: 17429624.

5./ Crotzer DR et al. Lack of effective systemic therapy for recurrent clear cell carcinoma of the ovary. Gynecol Oncol. 2007 May;105(2):404-8. Epub 2007 Feb 9. PubMed PMID: 17292461.

6./ Markman M. A Unique Role for Retrospective Studies in Clinical Oncology. Oncology. 2014;86(5-6):350. doi: 10.1159/000360911. Epub 2014 Jun 12. PubMed PMID:24942408.

7./ A Phase II Evaluation of Temsirolimus (CCI-779) (NCI Supplied Agent: NSC# 683864,) in Combination With Carboplatin and Paclitaxel Followed by Temsirolimus (CCI-779) Consolidation as First-Line Therapy in the Treatment of Stage III-IV Clear Cell Carcinoma of the Ovary. ClinicalTrials.gov Identifier: NCT01196429.

8./ A Phase II Evaluation of the Efficacy of Sunitinib® in Patients With Recurrent Ovarian Clear Cell Carcinoma. ClinicalTrials.gov Identifier: NCT01824615.

9./ A Phase II Study of Oral ENMD-2076 Administered to Patients With Ovarian Clear Cell Carcinomas. ClinicalTrials.gov Identifier: NCT01914510.

10./ A Phase II Trial of DCTD-Sponsored Dasatinib (NSC #732517) in Recurrent/Persistent Ovary, Fallopian Tube, Primary Peritoneal, and Endometrial Clear Cell Carcinoma Characterized for the Retention or Loss of BAF250a Expression. ClinicalTrials.gov Identifier: NCT02059265.

 

 

PBS Documentary, “The Whisper: The Silent Crisis of Ovarian Cancer.”

To raise ovarian cancer awareness, Long Island’s Public Broadcasting Service (PBS) affiliate WLIW-Channel 21 will present the exclusive New York metro area premiere of a half-hour television documentary entitled, “The Whisper: the silent crisis of ovarian cancer.” The program will debut at 7 P.M. (EDT) on Friday, September 24 in the New York metro area, and will be rolled out to other PBS affiliates across the country over the next 12 months.

More than 13,000 women this year will be struck down by ovarian cancer, which is the most lethal gynecologic cancer. Ovarian cancer statistics are staggering; nearly three out of every four women with this disease will die because of it. Chances of survival can improve if it is detected early and confined to the ovaries. Unfortunately, only about 25 percent of women are diagnosed with early stage disease because there is no reliable early stage screening test available. Victims of ovarian cancer include President Obama’s mother Ann Soetoro, Coretta Scott King and comedienne Gilda Radner.

To raise awareness of this devastating disease, Long Island’s Public Broadcasting Service (PBS) affiliate WLIW-Channel 21 will present the exclusive New York metro area premiere of a half-hour television documentary entitled, The Whisper: The Silent Crisis of Ovarian Cancer.  A preview trailer of the documentary is provided below.

The Whisper:  the silent crisis of ovarian cancer — PBS Documentary

The program will debut at 7 P.M. (EDT) on Friday, September 24, with encore presentations scheduled for 10:30 P.M. on Monday, September 27, and 11:30 P.M. on Friday, October 1. The program will be rolled out to other PBS affiliates across the country over the next 12 months.

The documentary was made possible by a generous grant from the Sonia L. Totino Foundation and the Rocco Totino family. Mr. Totino, a New York resident, lost his wife Sonia to ovarian cancer several years ago, and wished to honor her with an initiative that seeks to raise awareness among women of the warning signs of ovarian cancer, and by doing so, reduce the number of women lost to this devastating disease.

Sharon Blynn is the founder of Bald is Beautiful & the host of “The Whisper: the silent crisis of ovarian cancer” (a PBS documentary)

The host featured in the documentary is Sharon Blynn, who is an ovarian cancer survivor and the founder of the Bald Is Beautiful campaign. Through this campaign, Sharon wants to send a message to women that they can “flip the script” on the many traumatic aspects of the cancer experience, and embrace every part of their journey with self-love, empowerment, and a deep knowing that their beauty and femininity radiate from within and are not diminished in any way by the effects of having cancer.  As an “actorvist,” Sharon communicates the Bald Is Beautiful message through acting, writing, modeling and spokesperson appearances, and she continues to do patient outreach through one-on-one correspondence via her website, hospital visitations, being a chemo buddy and other such activities.

Other Bald Is Beautiful highlights include an international print campaign for the Kenneth Cole “We All Walk in Different Shoes” campaign, an international print and TV campaign for Bristol-Myers Squibb, appearances in “Sex and the City” and a principal role in Seal’s music video “Love’s Divine.” She has been featured in magazine and newspaper articles in Glamour, Vogue, Marie Claire (US & Italia), Organic Style, BUST, the Miami Herald and other publications. Sharon has also performed onstage as part of the “Off the Muff” collective, and she was commissioned to write and perform her one-woman theatrical piece “How Are We Feeling Today?” which saw its world premiere in Los Angeles and was presented in New York City. A QuickTime video compilation of Sharon’s past projects can be viewed here.

Blynn was awarded the prestigious 2010 Lilly Tartikoff/Entertainment Industry Foundation Hope Award at the 2010 National Coalition for Cancer Survivorship “Rays of Hope Gala” held in Washington, D.C. Sharon has also been selected to be part of Lifetime Television Network’s Every Woman Counts “Remarkable Women” campaign, and will appear in a 30-second spot that will run the week of Sept 17–23, 2010.

The nationally-renowned ovarian cancer experts featured in the documentary include:

Barbara A. Goff, M.D., Professor, Gynecologic Oncology, University of Washington School of Medicine. Dr. Goff is the principal investigator responsible for critical ovarian cancer research which revealed that ovarian cancer is generally accompanied by four primary warning signs or symptoms — bloating, pelvic or abdominal pain, difficulty eating or feeling full quickly, and urinary symptoms (urgency or frequency).  Goff’s research became the foundation for the Ovarian Cancer Symptoms Consensus Statement, which was sponsored and co-authored by the American Cancer Society, Gynecologic Cancer Foundation, and Society of Gynecologic Oncologists in July 2007.

Beth Y. Karlan, M.D., Board of Governors Endowed Chair, Director, Women’s Cancer Research Institute and Division of Gynecologic Oncology, Cedars-Sinai Medical Center; Professor, Obstetrics and Gynecology, David Geffen School of Medicine ,University of California, Los Angeles (UCLA). Dr. Karlan is a world-renowned expert in the field of gynecologic oncology, specifically ovarian cancer surgery, early detection, targeted therapies and inherited cancer susceptibility. She is a past-president of the Society of Gynecologic Oncologists, the Editor-in-Chief of Gynecologic Oncology, and has held many international leadership positions.  She is committed to both scientific advancement and enhancing public awareness about gynecologic cancers.

John Lovecchio, M.D., Chief of Gynecologic Oncology, North Shore-Long Island Jewish Health System; Leader of the North Shore-LIJ Cancer Institute; Professor of Obstetrics and Gynecology, the New York University School of Medicine.  Dr. Lovecchio’s major areas of research are in uterine and ovarian cancers, and he holds administrative and leadership positions in regional and national professional organizations and has published extensively in peer-reviewed journals. Lovecchio is widely regarded as a leading physician-surgeon and has received numerous awards in recognition of his academic and professional achievements.  In the documentary, Dr. Lovecchio offers his insight on ways to combat this deadly form of cancer. He is also credited as the technical advisor for the documentary.

Maurie Markman, M.D., Vice President of Patient Oncology Services & National Director of Medical Oncology, Cancer Treatment Centers of America.  For more than 20 years, Dr. Markman has been engaged in clinical research in the area of gynecologic malignancies, with a particular focus on new drug development and exploring novel management strategies in female pelvic cancers.  Dr. Markman’s many accomplishments include serving as Editor-In-Chief for the Current Oncology Reports journal and Oncology (Karger Publishers) journal, and serves as Chairman of the Medical Oncology Committee of the national Gynecologic Oncology Group.  In addition, Dr. Markman has served on numerous editorial boards, including the Journal of Clinical Oncology and Gynecologic Oncology.  Dr. Markman has been the primary author, or co-author, on more than 1,000 published peer-reviewed manuscripts, reviews, book chapters, editorials or abstracts, and he has edited or co-edited 14 books on various topics in the management of malignant disease, including Atlas of Oncology and the most recent edition of Principles and Practice of Gynecologic Oncology.

“Taking part in this program was a labor of love and concern for my patients,” said Dr. Lovecchio, who is based at North Shore University Hospital in Manhasset. “I wanted to make sure that women are getting the right information, and are aware of the signs and symptoms of ovarian cancer. They must be alert to their own bodies and recognize that abdominal bloating, abdominal pain, pelvic pain, urinary symptoms, difficulty in eating, and feeling full quickly may not be the norm.”

“I wanted to make sure that women are getting the right information, and are aware of the signs and symptoms of ovarian cancer. They must be alert to their own bodies and recognize that abdominal bloating, abdominal pain, pelvic pain, urinary symptoms, difficulty in eating, and feeling full quickly may not be the norm.”

— John Lovecchio, M.D., Chief of Gynecologic Oncology, North Shore-Long Island Jewish Health System

“Women should seek the advice of experts trained in this field and not think that they are being alarmists. Other medical experts and patients interviewed in this documentary are all seeking the same outcome — to make every woman aware of her own body and to encourage every woman to seek help if she feels that something is not quite right,” said Dr. Lovecchio, who was interviewed for the documentary along with Drs. Goff, Karlan, and Markman.

Source:  PBS Documentary on Ovarian Cancer, News Release, North Shore-Long Island Jewish Health System, September 9, 2010.

Non-Platinum Topotecan Drug Combination Therapy Provides No Survival Advantage Over Topotecan Monotherapy

“In women with recurrent ovarian cancer, treatment with topotecan along with etoposide or gemcitabine offers no survival advantage over topotecan monotherapy, German and Austrian researchers report in the July 1st issue of the Journal of Clinical Oncology.”

“In women with recurrent ovarian cancer, treatment with topotecan along with etoposide or gemcitabine offers no survival advantage over topotecan monotherapy, German and Austrian researchers report in the July 1st issue of the Journal of Clinical Oncology.

‘Combination therapies,’ lead investigator Dr. Jalid Sehouli told Reuters Health, ‘were associated with higher toxicity, but progression-free survival and overall survival were not significantly different.’

Dr. Sehouli, of Humboldt University in Berlin, and colleagues explain in their paper that although topotecan monotherapy is an established treatment, there was evidence to suggest that combination therapy may provide better results.

To investigate further, the researchers studied 502 women in whom ovarian cancer recurred following primary surgery and platinum-based chemotherapy. They were randomized to receive either topotecan alone or in combination with etoposide or gemcitabine.

Median overall survival was not significantly different among the groups: 17.2 months with topotecan alone, 17.8 months with the etoposide combination and 15.2 months with the gemcitabine combination. There were no differences in either median progression-free survival or objective response rates.

The researchers note that the incidence of thrombocytopenia was lower with monotherapy (13.5%) than with the etoposide combination (21.5%) or gemcitabine combination (31.3%), and they conclude that combination therapy increases toxicity and does not provide a survival advantage.

‘Based on our results,’ Dr. Sehouli warns, ‘physicians should not harm their patients with such combination regimens.’”

Quoted Source: Topotecan Combo No Extra Help in Ovarian Cancer, by David Douglas, Matria Healthcare News, July 28, 2008 (summarizing the findings of Nonplatinum topotecan combinations versus topotecan alone for recurrent ovarian cancer: results of a phase III study of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group; Sehouli J et. al., J Clin Oncol. 2008 July;26(19):3176-82.

Additional Information:

• Single-Agent Topotecan Still Best for Recurrent or Platinum-Resistant Ovarian Cancer (Video Presentation), by Maurie Markman, M.D., Vice President for Clinical Research, The University of Texas M.D. Anderson Cancer Center, Markman on Oncology Video, Medscape Hematology-Oncology, Medscape Today, July 28, 2008.