Complete clinical responses to cancer therapy caused by multiple divergent approaches: a repeating theme lost in translation

Complete clinical responses to cancer therapy caused by multiple diver

Complete clinical responses to cancer therapy caused by multiple divergent approaches: a repeating theme lost in translation (click on 'pdf' for full paper; references to ovarian cancer; hormonal therapy; angiogenesis...)

Abstract:
Over 50 years of cancer therapy history reveals complete clinical responses (CRs) from remarkably divergent forms of therapies (eg, chemotherapy, radiotherapy, surgery, vaccines, autologous cell transfers, cytokines, monoclonal antibodies) for advanced solid malignancies occur with an approximately similar frequency of 5%–10%. This has remained frustratingly almost static. 
However, CRs usually underpin strong durable 5-year patient survival. How can this apparent paradox be explained? 

Reply to W.R. Robinson from Chi: re: “Is the Easier Way Ever the Better Way? (ovarian cancer/neoadjuvant therapy/surgery/references...)

 Blogger's Note: follows to prior posting/correspondence/dialogue; worthwhile reading this discussion/debate, note the common denominator in references
           ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

Reply to W.R. Robinson

Reply to W.R. Robinson

1. Dennis S. Chi⇓

1. Memorial Sloan-Kettering Cancer Center, New York, NY

1. Corresponding author: Dennis S. Chi, MD, Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; e-mail: gynbreast@mskcc.org.

1. Robert E. Bristow

1. University of California, Irvine Medical Center, Orange, CA

1. Deborah K. Armstrong

1. Johns Hopkins Kimmel Cancer Center, Baltimore, MD

1. Beth Y. Karlan

+ Author Affiliations

1. Cedars-Sinai Medical Center, Los Angeles, CA

We thank Robinson¹ for his comments on our editorial, “Is the Easier Way Ever the Better Way?”² Robinson disagreed with our article on two points. First, he stated that it is “both disingenuous and unrealistic to… suggest that fellowship-trained, Board-certified gynecologic oncologists are not capable of operating on women with advanced ovarian cancer.” Robinson also expressed concern that we were suggesting that neoadjuvant chemotherapy (NACT) “somehow represents a failure on the part of the physicians who are taking ‘the easy way out.'”

To the first point, we did not say that fellowship-trained, Board-certified gynecologic oncologists are not capable of operating on women with advanced ovarian cancer. Rather, we wanted to highlight that the number of patients who receive suboptimal debulking could be reduced by collaboration with other surgical colleagues. Many gynecologic oncologists partner with urologists for complex continent urinary conduits after pelvic exenteration and with plastic surgeons for a myocutaneous flap after radical pelvic surgery, for example, and we believe that patients with ovarian cancer should also be offered the potential benefit of subspecialty surgical consultation if it will improve their overall survival. The complexity of preplanning surgical consultations for advanced ovarian cancer debulking surgery should not be any different than for these other surgical collaborations.

It is incumbent on the gynecologic oncologist to ensure that pressures to minimize operating room and intensive care unit usage do not compromise the surgical outcome for our patients.........

The author(s) indicated no potential conflicts of interest.

Previous Section

 

REFERENCES

1. ↵
   1. Robinson WR

   (2012) Neoadjuvant chemotherapy is rarely the easy way out. J Clin Oncol 30:1563.

   FREE Full Text
2. ↵
   1. Chi DS,
   2. Bristow RE,
   3. Armstrong DK,
   4. et al.

   (2011) Is the easier way ever the better way? J Clin Oncol 29:4073–4075.

   FREE Full Text
3. ↵
   1. Chi DS,
   2. Musa F,
   3. Dao F,
   4. et al.

   (2012) An analysis of patients with bulky advanced stage ovarian, tubal, and peritoneal carcinoma treated with primary debulking surgery (PDS) during an identical time period as the randomized EORTC-NCIC trial of PDS vs neoadjuvant chemotherapy (NACT) Gynecol Oncol 124:10–14.

   CrossRefMedline
4. ↵
   1. Vergote I,
   2. Tropé CG,
   3. Amant F,
   4. et al.

   (2010) Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med 363:943–953.

   CrossRefMedline
5. ↵
   1. Tiersten AD,
   2. Liu PY,
   3. Smith HO,
   4. et al.

   (2009) Phase II evaluation of neoadjuvant chemotherapy and debulking followed by intraperitoneal chemotherapy in women with stage III and IV epithelial ovarian, fallopian tube or primary peritoneal cancer: Southwest Oncology Group Study S0009. Gynecol Oncol 112:444–449.

   CrossRefMedline
6. ↵
   1. Chi DS,
   2. Eisenhauer EL,
   3. Zivanovic O,
   4. et al.

   (2009) Improved progression-free and overall survival in advanced ovarian cancer as a result of a change in surgical paradigm. Gynecol Oncol 114:26–31.

   CrossRefMedline

Correspondence: Neoadjuvant Chemotherapy (ovarian cancer) Is Rarely the Easy Way Out + references +discussion on gyn specialists/general surgeons

Blogger's Note: worthwhile reading/pondering...
             ~~~~~~~~~~~~~

Neoadjuvant Chemotherapy Is Rarely the Easy Way Out

 To the Editor:

I appreciate the thoughtful analysis by Chi et al¹ in the November 1 issue of Journal of Clinical Oncology, in the article entitled, “Is the Easier Way Ever the Better Way?” Chi et al make a very literate argument against using neoadjuvant chemotherapy (NACT) for ovarian cancer, continuing a discussion that has lingered among oncologists for more than 25 years. The argument has heated up recently as a result of several prospective studies, particularly that of Vergote et al,² which showed no difference in survival in patients treated with either primary surgery or NACT.

I must, however, disagree with Chi et al¹ on two points. The first of these is the suggestion by the authors that patients with stage IIIC/IV ovarian cancer should routinely be referred to ultraspecialist centers that are capable of performing advanced upper abdominal surgery. In reality, the great majority of patients with ovarian cancer in the United States have been and will be treated in community settings for the foreseeable future. The professional societies that represent gynecologic oncology have for years strongly recommended that ovarian cancer be handled by fellowship-trained gynecologic oncologists. This effort has met with mixed success; in many communities it is still the norm for women with advanced ovarian cancer to be operated on by physicians with no special oncologic surgical training.......

plus references:

REFERENCES

1. ↵
   1. Chi DS,
   2. Bristow RE,
   3. Armstrong DK,
   4. et al.

   (2011) Is the easier way ever the better way? J Clin Oncol 29:4073–4075.

   FREE Full Text
2. ↵
   1. Vergote I,
   2. Tropé GC,
   3. Amant F,
   4. et al.

   (2010) Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med 363:943–953.

   CrossRefMedline
3. ↵
   1. Tiersten AD,
   2. Liu PY,
   3. Smith HO,
   4. et al.

   (2009) Phase II evaluation of neoadjuvant chemotherapy and debulking followed by intraperitoneal chemotherapy in women with stage III and IV epithelial ovarian, fallopian tube or primary peritoneal cancer: Southwest Oncology Group Study S0009. Gynecol Oncol 112:444–449.

   CrossRefMedline

MD News - HIPEC: Furthering Survivorship for GYN Cancer Patients

MD News - HIPEC: Furthering Survivorship for GYN Cancer Patients

Monday, March 12, 2012

A team of cancer specialists at the Seidman Cancer Center at University Hospitals (UH) Case Medical Center is among the first in the nation to launch a dedicated gynecologic program using Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to treat ovarian, endometrial and select other malignancies.

 Q: What is HIPEC, and how is it delivered?
Q: What are the advantages of HIPEC over traditional IV chemotherapy?
Q: I understand UH is planning several research studies on HIPEC. What will they involve?
Q: What do you want physicians to know about HIPEC?
   

abstract: Percutaneous Insertion of (IP) Peritoneal Ports (study = 29 women)

Objective: To describe a technique for image-guided percutaneous insertion of peritoneal ports in patients without ascites who have undergone surgical debulking for stage III ovarian cancer.

Conclusions: Placement of percutaneous intraperitoneal ports is feasible with an acceptably low complication rate of 6.9% in patients without abdominal ascites.

Chemotherapy Options in the Management of Platinum-Sensitive Recurrent Ovarian Cancer

Note: registration required to view (free) SPECIAL EDITION / EDUCATIONAL REVIEWS

ISSUE: AUGUST, 2010 | VOLUME: 05:08 Chemotherapy Options in the Management of Platinum-Sensitive Recurrent Ovarian Cancer

abstract: Continued chemotherapy after complete response to primary therapy among women with advanced ovarian cancer (meta-analysis)

CONCLUSIONS

Although individual studies have not yet convincingly shown a survival advantage with maintenance chemotherapy in OC, this meta-analysis demonstrates that continued chemotherapy after completion of primary therapy for OC improves PFS and OS. Benefits are greatest in patients with advanced stage OC who reach complete clinical or pathologic response after primary therapy.

Is adjuvant chemotherapy indicated in stage I pure immature ovarian teratoma (IT)? A multicentre Italian trial in ovarian cancer

CONCLUSIONS.: Our study suggests that chemotherapy may be withheld for primary therapy and utilized only for recurrence.

Chemotherapy resistant ovarian tumour cells "re-grow" cancer - media UK

"Shielded" ovarian cancer cells may survive chemotherapy. "The researchers compared the characteristics of cell lines from the tumour at the time of diagnosis to cell lines from the same patients once the disease had been treated and become resistant." ""By examining the characteristics of ovarian tumours we now think that cells resistant to chemotherapy grow as part of the tumour. This means that when patients have treatment, cells that respond to chemotherapy are destroyed but this leaves behind resistant cells which then form another tumour of completely resistant cells. This seems to explain why successful treatment for relapsed patients is difficult. What needs to be developed now is a therapy designed to target the resistant cells.""

IU-OSU center gets $9 million more for cancer epigenetics: IU News Room: Indiana University (includes ovarian cancer)

"Over the next five years, Nephew said the OSU/IU-led team will study epigenetic changes in prostate, breast, and ovarian cancer cells that cause resistance to hormonal therapy or traditional chemotherapy. Nephew said a major objective is to identify a panel of epigenetic biomarkers for predicting responsiveness to anti-hormone treatments and chemotherapies in cancer patients."

full access: Tumor Angiogenesis: Insights and Innovations (not specific to ovarian cancer)

"These two ongoing theories showcase the current problems in the field of antiangiogenic research in cancer. After several years of clinical trials, it appears that targeting one angiogenic factor is not enough to permanently halt neovascularization in most tumors. Although these results were initially disheartening, they also opened up the possibility of other angiostatic therapies.
Many clinical trials now use existing chemotherapeutic drugs or radiation along with antiangiogenic drugs. This two-front attack has had more
success than antiangiogenic drugs or chemotherapy alone in a majority of patients."

(U.S.)Impact of a chemoresponse assay on treatment costs recurrent ovarian cancer

Abstract

OBJECTIVE: We sought to estimate mean costs of chemotherapy treatment for recurrent ovarian cancer with or without use of a chemoresponse assay.
STUDY DESIGN: We estimated mean costs for 3 groups: (1) assay assisted: 75 women who received oncologist's choice of chemotherapy following chemoresponse testing (65% adherence to test results), (2) assay adherent: modeled group assuming 100% adherence to assay results, and (3) empiric: modeled from market share data on most frequently utilized chemotherapy regimens. Cost estimates were based on commercial claims database reimbursements.
RESULTS: The most common chemotherapy regimens used were topotecan, doxorubicin, and carboplatin/paclitaxel. Mean chemotherapy costs for 6 cycles were $48,758 (empiric), $33,187 (assay assisted), and $23,986 (assay adherent). The cost savings related to the assay were associated with a shift from higher- to lower-cost chemotherapy regimens and lower use of supportive drugs such as hematopoiesis-stimulating agents.
CONCLUSION: Assay-assisted chemotherapy for recurrent ovarian cancer may result in reduced costs compared to empiric therapy.

Combination versus sequential cytotoxic chemotherapy in recurrent ovarian cancer: Time for an evidence-based comparison

Note: no abstract/subscriber based journal ($$)
Combination versus sequential cytotoxic chemotherapy in recurrent ovarian cancer: Time for an evidence-based comparison.
Markman M

Identification of early predictive imaging biomarkers and their relationship to serological angiogenic markers in patients with ovarian cancer with residual disease following cytotoxic therapy

Note: small study  
Background: Patients with recurrent ovarian cancer often achieve partial response following chemotherapy, resulting in persistent small volume disease. After completion of treatment, the dilemma of when to initiate subsequent chemotherapy arises. Identification of biomarkers that could be used to predict when subsequent treatment is needed would be of significant benefit. Design: ...A subgroup of patients provided plasma (blood) samples within which a panel of angiogenic biomarkers was quantified.  

New Joint Outpatient Chemotherapy Administration Standards - Cancer Journal for Clinicians

The guidelines were created largely in response to recent studies that have examined reports of chemotherapy administration errors among outpatients, and to reports of an increased risk of errors with the administration of new oral chemotherapeutics.

Regional abdominal hyperthermia combined with systemic chemotherapy for the treatment of patients with ovarian cancer relapse: Results of a pilot stud

Note: warning on stats

"Results: Overall, 36 OCR patients were enrolled. The majority of the patients (>80%) were classified as platinum resistant.....
Prospective phase III trials are warranted to evaluate the benefit and efficacy in heavily pre-treated patients with OCR."

videos: The Chemotherapy Foundation Symposium

Note: there are some key videos (free to view) from a variety of subjects

Meeting Archives

Chemotherapy Foundation Symposium XXVI
November 4 -8, 2008
Marriott Marquis Hotel , New York , NY

Innovative Cancer Therapy for Tomorrow

Chemotherapy-induced nausea and vomiting: contemporary approaches to optimal management

abstract 5/2009: MicroRNAs and their target messenger RNAs associated with ovarian cancer response to chemotherapy

Markman: Intraperitoneal chemotherapy in the management of ovarian cancer: focus on carboplatin

article: http://www.dovepress.com/intraperitoneal-chemotherapy-in-the-management-of-ovarian-cancer-focus-peer-reviewed-article

open text pdf file: http://www.dovepress.com/getfile.php?fileID=4267

Worth noting:

Finally, as it is known that patients with “high risk”
early stage ovarian cancer have a 30% to 50% chance of
experiencing recurrence of the disease process, and those
recurrences are largely within the peritoneal cavity, it is
perhaps reasonable to consider delivering some, or perhaps
all, of a planned adjuvant chemotherapy approach via the
intraperitoneal route.