Cancer Treatment Today » Esophageal Cancer

Avastin for neaodjuvant treatment or for metastatic esophageal cancer – pro

M Levin, MD — Thu, 06 Sep 2012 00:37:30 +0000

For esophageal cancer, bevacizumab is in the early stages of clinical development. Most trials have been limited to GE adenocarcinomas, given the life-threatening hemoptysis described in bevacizumab-treated patients with squamous cell carcinoma of the lung. A multi-center phase II study of irinotecan, cisplatin, and bevacizumab in 20 patients with unresectable or metastatic gastric or GE adenocarcinoma has shown encouraging preliminary results. Shah and colleagues reported an 87% control rate (PR/SD). Of the 10 patients with measurable disease who completed at least two cycles, the investigators reported PRs in five (50%), minor PRs in four (40%), and stable disease in one. The combination therapy was well tolerated, although, as detailed in a recent update, six (25%) of 24 patients developed thromboembolic events, one patient had a gastric perforation, and another had a near perforation on imaging. No patients had significant bleeding.
Given that most patients with locally advanced esophageal cancer are treated with concurrent chemoradiation, there may be a possible integrative role for VEGF blockade. Neoadjuvant chemoradiation has a minimal effect on the angiogenic tumor profile (VEGF, von Willebrand factor, CD68, macrophage infiltration), portending a bad prognosis. VEGF blockade reduces tumor interstitial pressure and vascular permeability, thus enhancing radiation and delivery of chemotherapy to tumors.he radiosensitizing effect of VEGF antibody has been demonstrated in several xenograft models, including those of glioma, colon, lung, and esophageal adenocarcinomaVEGF antibody with radiation induced supra-additive tumor growth delay and sustained cell death over a significant period of time in vivo (4–6 months) without schedule dependency . Moreover, radiation potentiation occurred under both hypoxic and normal tumor oxygenation. These preclinical data were explored further in a recent phase I rectal cancer clinical trial with neoadjuvant 5-FU, radiation, and bevacizumab. The addition of bevacizumab to concurrent chemoradiotherapy was feasible and had no significant additive toxicities. A preoperative trial with bevacizumab, cisplatin, irinotecan, and concurrent radiation in locally advanced esophageal adenocarcinoma is open at Memorial Sloan-Kettering Cancer Center later this year.

There is not sufficient credible evidence and no guidelines recommendations to consider Avastin medically necessary in combination or alone for esophageal cancer.

J. Wang, F. Liu, H. Gao, W. Wei, X. Zhang, Y. Liang, and Y. Cheng he Symptom-to-Treatment Delay and Stage at the Time of Treatment in Cancer of Esophagus pn. J. Clin. Oncol., February 5, 2008; (2008)

Shah MA, Ilson D, Saltz E et al. A multicenter phase II study of irinotecan(CPT), cisplatin(CIS), and bevacizumab(BEV) in patients with unresectable or metastatic gastric or gastroesophageal(GEJ) adenocarcinoma. Proc Am Soc Clin Oncol 2005;23:314s.

Shah MA, Ilson D, Kelsen DP. Thromboembolic events in gastric cancer: high incidence in patients receiving irinotecan- and bevacizumab-based therapy. J Clin Oncol 2005;23:2574–2576.

J. Tabernero , T. Macarulla , F. J. Ramos , and J. Baselga
Novel targeted therapies in the treatment of gastric and esophageal cancer
Ann Oncol 16: 1740-1748.

PET for esophageal cancer – pro

M Levin, MD — Thu, 06 Sep 2012 00:36:23 +0000

The imaging modalities commonly used for the diagnosis and staging of esophageal cancer are upper GI study, endoscopy, endoscopic ultrasound, CT, and PET.
PET is superior to CT and EUS combined in diagnosing stage IV disease. NCCN recommends PET for preoperative staging only, not for restaging. While the studies on detection of distant disease suggest better diagnostic performance for PET over CT, the available body of evidence is small. Only one study clearly avoided verification bias, only one clearly interpreted PET blind to the reference standard, and none clearly interpreted the reference standard blind to PET. Various TEC Assessments have not recommended PET for restaging. More recently ESMO says in the same vein : “Moreover, PET (or PET-CT) may be helpful in identifying otherwise undetected distant metastases [II, B]“. Other recent articles support PET for restaging.

John F. Bruzzi, FFRRCSI, Reginald F. Munden, MD, Mylene T. Truong, MD, Edith M. Marom, MD, Bradley S. Sabloff, MD, Gregory W. Gladish, MD, Revathy B. Iyer, MD, Tin-Su Pan, PhD, Homer A. Macapinlac, MD and Jeremy J. Erasmus, MD PET/CT of Esophageal Cancer: Its Role in Clinical Management, 2007 RadioGraphics, 27, 1635-1652.

NCCN, Esophageal ESOPH-18, 2016

M. Stahl, C. Mariette, K. Haustermans, A. Cervantes, D. Arnold Oesophageal Cancer: ESMO Clinical Practice Guidelines, Ann Oncol 2013; 24 (Suppl 6): vi51-vi56.

Flamen P, Van Cutsem E, Lerut A, Cambier JP, Haustermans K, Bormans G, De Leyn P, Van Raemdonck D, De Wever W, Ectors N, Maes A, Mortelmans L. Positron emission tomography for assessment of the response to induction radiochemotherapy in locally advanced oesophageal cancer. Ann Oncol. 2002 Mar;13(3):361-8.

Wong R, Walker-Dilks C. PET imaging in esophageal cancer: recommendations. Toronto (ON): Cancer Care Ontario (CCO); 2009 Jan 19. 27 p. (Recommendation report – PET; no. 4). [44 references]

Sun L, Su XH, Guan YS, Pan WM, Luo ZM, Wei JH, Zhao L, Wu H. Clinical usefulness of 18F-FDG PET/CT in the restaging of esophageal cancer after surgical resection and radiotherapy. World J Gastroenterol. 2009 Apr 21;15(15):1836-42.

Adjuvant chemoradiation for esophageal cancer – pro

M Levin, MD — Thu, 06 Sep 2012 00:34:24 +0000

Carcinoma of the esophagus is an aggressive malignancy with an increasing incidence. Its virulence, in terms of symptoms and mortality, justifies a continued search for optimal therapy. A recent clincial guidelines concluded: ” In consideration of the systematic review, external review, and subsequent Practice Guidelines Coordinating Committee revision suggestions, and final approval, the Gastrointestinal Cancer Disease Site Group recommends the following:For adult patients with resectable thoracic esophageal cancer for whom surgery is considered appropriate, surgery alone (i.e., without neoadjuvant or adjuvant therapy) is recommended as the standard practice.” This is also the conclusion of the Ontario Evidence Based Program based on the same evidence, except that it accepts preoperative chemotherapy but not adjuvant postop therapy.

Other guidelines disagree. NCCN recommends fluorpyrimidine based chemo radiation for T2 and T3, N0 or node positive disease. It defines it as 5FU or capecitabine, without leukovorin and also recommends pre and postoperative ECF.

Malthaner RA, Wong RK, Rumble RB, Zuraw L; Gastrointestinal Cancer Disease Site Group of Cancer Care Ontario’s Program in Evidence-based Care. Neoadjuvant or adjuvant therapy for resectable esophageal cancer: a clinical practice guideline. BMC Cancer. 2004 Sep 24;4:67.

Malthaner RA, Wong RK, Rumble RB, Zuraw L; Members of the Gastrointestinal Cancer Disease Site Group of Cancer Care Ontario’s Program in Evidence-based Care. Neoadjuvant or adjuvant therapy for resectable esophageal cancer: a systematic review and meta-analysis.BMC Med. 2004 Sep 24;2:35.

http://www.cancercare.on.ca/pdf/pebc2-11f.pdf

NCCN.Esophageal

Cascinu S, Labianca R, Barone C, et al. Adjuvant treatment of high-risk, radically resected gastric cancer patients with 5-fluorouracil, leucovorin, cisplatin, and epidoxorubicin in a randomized controlled trial. J Natl Cancer Inst 2007; 99:601.

Sun P, Xiang JB, Chen ZY. Meta-analysis of adjuvant chemotherapy after radical surgery for advanced gastric cancer. Br J Surg 2009; 96:26.

Locally advanced esophageal and GE Junction cancer: Chemotherapy and radiation including paclitacel and carboplatin – pro

M Levin, MD — Thu, 06 Sep 2012 00:33:04 +0000

Esophageal cancer, including cancer arising from the gastro-esophageal junction, is a challenging disease worldwide. At diagnosis, approximately 50% of patients present with disease that extends beyond the site of origin in the esophagus. The Radiation Therapy Oncology Group (RTOG) study 85-01 compared treatment with 4 cycles of cisplatin plus 5-FU with radiation therapy (50 Gy in 25 fractions) to radiation therapy (64 Gy in 32 fractions) in patients with local-regional thoracic esophageal cancer (T1-3, N0-1, M0) (23) Ninety percent of the patients had squamous cell carcinoma. Patients treated with both chemotherapy and radiation therapy had a significantly better average duration of survival (14 months vs 9 months, p < 0.0001) and more of these patients were alive 5 years after treatment (27% vs 0 %, p < 0.0001). Combined chemotherapy plus radiotherapy became the new standard of care for patients with esophageal cancer that was not amenable to surgical removal. At this point, several other chemo regimens have been studied and are consdired standard with radiation, among them capecitabine as noted above.

A study by Horning et al showed that DFS and OS for carboplatin/paclitaxel compared with cisplatinum/5-FU as dCRT treatment in EC patients. Toxicity rates were lower in the carboplatin/paclitaxel group together with higher treatment compliance. A study by El-Rayes found that the combination of carboplatin and paclitaxel is an moderately active and tolerable regimen in advanced esophageal cancer.

DeNittis AS. Esophagus. In: Perez CA, Brady LW, Halperin EC (eds): Principles and Practice of Radiation Oncology. 4th edition. Lippincott Williams & Wilkins. 2004, pp 1282-1305.

B. F. El-Rayes, A. Shields, M. Zalupski, L. K. Heilbrun, V. Jain, D. Terry, A. Ferris and P. A. Philip. A phase II study of carboplatin and paclitaxel in esophageal cancer. Ann Oncol (2004) 15 (6): 960-965.

M. Stahl, C. Mariette, K. Haustermans, A. Cervantes, D. Arnold, Oesophageal Cancer: ESMO Clinical Practice Guidelines Ann Oncol 2013; 24 (Suppl 6): vi51-vi56.
J. Honing; J. K. Smit; C. T. Muijs; J. G. M. Burgerhof; J. W. de Groot; G. Paardekooper; K. Muller; D. Woutersen; M. J. C. Legdeur; W. E. Fiets; A. Slot; J. C. Beukema; J. Th. M. Plukker; G. A. P. HospersA Comparison of Carboplatin and Paclitaxel With Cisplatinum and 5-Fluorouracil in Definitive Chemoradiation in Esophageal Cancer Patients. Ann Oncol. 2014;25(3):638-643.

Evidence-based Series #2-11 Version 2.2008: Section 1
Preoperative or Postoperative Therapy for Resectable Esophageal Cancer: Guideline Recommendations
RA Malthaner, RKS Wong, K Spithoff, RB Rumble, L Zuraw,
and the Gastrointestinal Cancer Disease Site Group
A Quality Initiative of the
Program in Evidence-based Care (PEBC), Cancer Care Ontario (CCO)
Report Date: May 21, 2008

J. Honing; J. K. Smit; C. T. Muijs; J. G. M. Burgerhof; J. W. de Groot; G. Paardekooper; K. Muller; D. Woutersen; M. J. C. Legdeur; W. E. Fiets; A. Slot; J. C. Beukema; J. Th. M. Plukker; G. A. P. HospersA Comparison of Carboplatin and Paclitaxel With Cisplatinum and 5-Fluorouracil in Definitive Chemoradiation in Esophageal Cancer Patients. Ann Oncol. 2014;25(3):638-643.

M. Stahl et al, Esophageal cancer: Clinical Practice Guidelines for diagnosis, treatment and follow-up
and On behalf of the ESMO Guidelines Ann Oncol (2010) 21 (suppl 5): v46-v49.

nccn.org, Esophageal, 2017

Vinorelbine/ cisplatin for esophageal cancer – pro

M Levin, MD — Thu, 06 Sep 2012 00:32:02 +0000

The vinorelbine/ cisplatin combination for esophageal cancer is based on Phase II data, more specifically on one phase II study. The authors concluded that, “…vinorelbine and cisplatin in combination constitutes an active regimen for patients with metastatic squamous cell carcinoma of the oesophagus with response rates similar to the better treatment in the previous EORTC randomised study (34% for vinorelbine–cisplatin compared with 35% for cisplatin–5-FU), while substantially reducing the level of fatal treatment-related toxicity. This 2-day regimen is also more convenient for patients than the 5-day cisplatin–5-FU combination. However, given the long duration of the trial and decline of the incidence of squamous cell oesophageal carcinoma in North America and some Western European countries, no further development of this combination is scheduled within the EORTC.”. One can argue that since it is not being explored farther, it should nto be considered investigtioanl; however, a more correct conclusion is that it needs to be studied more but will not be for reasons outside of its experimetnal status.

Delord, J. P et al, A dose-finding study of gemcitabine and vinorelbine in advanced previously treated malignancies.Annals of Oncology. 11(1):73-79, January 2000.

T. Conroy , P.-L. Etienne , A. Adenis , M. Ducreux , B. Paillot , J. Oliveira , J.-F. Seitz , E. Francois , E. Van Cutsem , D. J. T. Wagener , F. Kohser , S. Daamen , M. Praet , T. Gorlia , B. Baron , and J. Wils
Vinorelbine and cisplatin in metastatic squamous cell carcinoma of the oesophagus: response, toxicity, quality of life and survival
Ann Oncol 13: 721-729.

Tarceva for esophageal cancer – pro

M Levin, MD — Thu, 06 Sep 2012 00:31:01 +0000

Erlotinib has shown activity individually, as single drugs, or in combination with chemotherapy in upper gastro-intestinal cancers, including esophageal and gastro-esophageal adenocarcinomas, gastric cancer and pancreatic cancer. In several recent phase 2 trials,erlotinib appears to be somewhat active in esophageal cancer and not very active in gastric cancer. The authors conclude that additional studies with erlotinib as a single agent and in combination with other targeted agents are warranted in this disease. Several such studies are in fact listed on the clinicaltrials.gov will be website. Tarceva is not listed by NCCN for esophageal cancer.
Tomislav Dragovich, Sheryl McCoy, Cecilia M. Fenoglio-Preiser, Jiang Wang, Jacqueline K. Benedetti, Amanda F. Baker, Christopher B. Hackett, Susan G. Urba, Ken Phase II Trial of Erlotinib in Gastroesophageal Junction and Gastric Adenocarcinomas: SWOG 0127

JCO October 20, 2006 vol. 24 no. 30 4922-4927

Dragovich T, Huberman M, Von Hoff DD, Rowinsky EK, Nadler P, Wood D, Hamilton M, Hage G, Wolf J, Patnaik A. Erlotinib plus gemcitabine in patients with unresectable pancreatic cancer and other solid tumors: phase IB trial. Cancer Chemother Pharmacol. 2007 Jul;60(2):295-303. Epub 2006 Dec 6.

Esophageal and Esophagogastric Junction Cancers
J Natl Compr Canc Netw Aug 1, 2011:830-887

Preoperative chemotherapy for esophageal cancer – pro

M Levin, MD — Wed, 05 Sep 2012 14:22:41 +0000

Lay Summary: Chemotherapy or chemotherapy with radiation are standard of care for esophageal cancer that has not spread.

The role of preoperative chemoradiation for esophageal cancer is well established. Two meta-analyses comprised of the results from 15 randomized controlled trials, as well as pooling performed by the Gastrointestinal Cancer Disease Site Group, all detected a statistically significant difference in survival favouring preoperative chemoradiotherapy, but at three years only. Therefore, the Gastrointestinal Cancer Disease Site Group acknowledges there is evidence indicating survival benefits with either neoadjuvant chemotherapy or chemoradiotherapy compared with surgery alone; however, individual trial results are inconsistent. Based on the majority of the evidence available at this time, the Gastrointestinal Cancer Disease Site Group continues to support the stated recommendations and will continue to examine new evidence as it becomes available. NCCN does list chemoradiation for resectable esophageal cancer. It lists cisplatin/5FU or a “taxane based regimen” as acceptable alternatives. On p.18, NCCN notes that leukovorin is indicated in certain infusional 5FU regimens.

Malthaner RA, Collin S, Fenlon D. Preoperative chemotherapy for resectable thoracic esophageal cancer. Cochrane Database of Systematic Reviews 2001, Issue 1

nccn.org, esophageal cancer

Xelox for esophageal cancer – pro

M Levin, MD — Tue, 04 Sep 2012 17:48:53 +0000

There had recently been much evolution in the treatment of esophageal cancer. Among changes has been greater recognition of Xeloda and of Oxapliplatin as effective drugs. Ths isbased on thhREAL trial. The REAL trial enrolled 1,002 patients with locally advanced (inoperable) or metastatic cancer of the esophagus, esophagogastric junction, or stomach.

Patients were assigned to one of four treatment groups:

ECF (Ellence® (epirubicin), cisplatin, and 5-FU)
ECX (Ellence, cisplatin, and Xeloda)
EOF (Ellence, Eloxatin, and 5-FU)
EOX (Ellence, Eloxatin, and Xeloda)
One-year survival was 37.7% for ECF, 40.8% for ECX, 40.4% for EOF, and 46.8% for EOX.

Progression-free survival and response rates did not differ significantly across treatment groups. Overall survival was longer with EOX than with ECF.

In response to favorable Phase III trials (ML 17032 and REAL 2), the NCCN recently added oral fluoropyrimidine, Capecitabine (Xeloda®, Roche) as an option for treatment of esophageal and gastric cancer. The REAL 2 study, the largest ever phase III study in advanced esophageal and gastric cancer, found that Capecitabine may replace 5-FU and Oxaliplatin may replace Cisplatin in triplet regimens used for the treatment of advanced esophageal and gastric cancer. Thus, Xelox should be cosndiered appropriate for esophageal cancer.
Cunningham D, Starling N, Rao S et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. New England Journal of Medicine. 2008;358:36-46.

R. Quek, W. T. Lim, K. F. Foo, W. H. Koo, H. C. Toh Capcitabine and oxaliplatin (XELOX) in the treatment of advanced gastric cancer.Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 14089

nccn.org, esophageal 2012

Erbitux for esophageal cancer – pro

M Levin, MD — Mon, 03 Sep 2012 02:17:06 +0000

More than 50% of patients with esophageal cancer have metastatic disease at presentation. The use of chemotherapy for this patient group is increasing with the intention of local and distant tumor control, improving quality of life and prolongation of survival. A number of agents have been investigated as sole therapy for esophageal cancer, including cisplatin, irinotecan, bleomycin, mitomycin, 5-fluorouracil, paclitaxel, methotrexate, vinorelbine, mitoguazone, vindesine, doxorubicin, and etoposide. Phase II trials have demonstrated responses of 15% to 30% for these agents, with cisplatin, mitomycin, 5-fluorouracil, paclitaxel, and vindesine being the most active. The responses have been short lived and have not led to any meaningful prolongation of survival. Five randomized controlled trials have not shown prolonged survival but occasional palliation can be achieved. There is a need for well designed, adequately powered, phase III trials comparing chemotherapy versus best supportive care for patients with metastatic esophageal cancer. Chemotherapy agents with promising response rates and tolerable toxicity are cisplatin, 5-fluorouracil (5-FU), paclitaxel and antracyclins. Combining taxotere and Xeloda is not supported by significant literature.

NCCN lists options for metastatic disease in a carefully worded way (without addressing specific protocols), with recommendations for oxaliplatin, cisplatin, 5FU, taxane or irinotecan (Camptosar) based therapy.

We eagerly await the results of the many cooperative group and single-institution clinical trials exploring the role of cetuximab in esophageal cancer. These include a South-west Oncology Group (SWOG) trial of cetuximab as second-line therapy in patients with metastatic esophageal adenocarcinoma, a Memorial Sloan-Kettering Cancer Center study of cetuximab in irinotecan/cisplatin-refractory patients with metastatic esophageal cancer and a Dana-Farber Cancer Institute preoperative trial with cisplatin, irinotecan, cetuximab, and radiation in locally advanced esophageal cancer. In two phase I studies, EGFR-directed antibodies have shown activity in patients with esophageal cancer. In the phase I study of the humanized EGFR mAb EMD72000, one patient with metastatic, pretreated squamous cell carcinoma had a durable, 6-month PR. In addition, a phase I trial with ABX-EGF, a high-affinity, fully human IgG2 EGFR mAb, reported stable disease for 7 months in one esophageal cancer patient. Two recent studies presented at the 2006 meeting of the American Society for Therapeutic Radiation and Oncology (ASTRO) suggest that Erbitux® (cetuximab) can be safely added to combination chemotherapy regimens for rectal and esophageal cancer. However, these are studies with radiation and in early phase II. At ASCO 2011, a French group rpesented a study of Folfox with Erbitux. The treatment was two cycles of FOLFOX induction therapy plus cetuximab, followed by radiotherapy at 50.4 Gy with FOLFOX. Cetuximab, 250 mg/m², was given weekly during induction and during the three cycles of chemoradiotherapy.

Results are summarized in the table. NCCN(ESOPH-E,3) lists various irinotecan. taxane platin combinations and does list Erbitux for second line to be combined with other regimens. This is level 2B recommendation.

(The Cochrane Database of Systematic Reviews 2006 Issue 4 Chemotherapy for metastatic (spread to other parts of the body) cancer which originates in the esophagus.

Malthaner R, Fenlon D. Preoperative chemotherapy for resectable thoracic esophageal cancer. Cochrane Database Syst Rev 2003;(4):CD001556.

NCCN.ORG, Esophageal Cancer

Tew, William P. , Kelsen, David P. , Ilson, David H.
Targeted Therapies for Esophageal Cancer
Oncologist 2005 10: 590-601;

Roedel C, Arnold D, Hipp M, et al. Cetuximab in combination with capecitabine, oxaliplatin and concomitant radiotherapy (Cet-Capox-RT) as preoperative therapy for rectal cancer. International Journal of Radiation Oncology* Biology*Physics. 2006;66, issue 3, Supplement:S82-S83, abstract 147.

Suntharalingam M, Dipretrillo T, Wanebo H, et al. A phase II trial evaluating the efficacy of weekly cetuximab, paclitaxel, carboplatin and daily RT in esophageal cancer. International Journal of Radiation Oncology* Biology*Physics. 2006;66, issue 3, Supplement:S22-S23, abstract 40.

Lledo G, Michel P, Dahan L, et al: Chemoradiation with FOLFOX plus cetuximab in locally advanced cardia or esophageal cancer: Final results of a GERCOR phase II trial (ERaFOX). 2011 Gastrointestinal Cancers Symposium. Abstract 8. Presented by Aimery de Gramont, MD, January 20, 2011.Figlin RA, Belldegrun AS, Crawford J et al. ABX-EGF, a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) in patients with advanced cancer: phase 1 clinical results. Proc Am Soc Clin Oncol 2002;21:10a.

William P. Tew, David P. Kelsen, David H. Ilson Targeted Therapies for Esophageal Cancer The Oncologist, Vol. 10, No. 8, 590-601, September 2005;

J. Tabernero*, T. Macarulla, F. J. Ramos and J. Baselga Novel targeted therapies in the treatment of gastric and esophageal cancer Annals of Oncology 2005 16(11):1740-1748;

Revised: 8/2/2011

Chemosensitivity and chemoresistance assays – pro

admin — Sun, 02 Sep 2012 14:32:16 +0000

Chemosensitivity assays are controversial but most experts believe that they do not reliably assist in selecting chemotherapy. There is more evidence for chemoresistance assays but this also remains disputed.

Chemoresistance assays are a modification that tests resistance to chemo rather than sensitivity. They work on the assumption that if celss show reesistance to very high concentrations of a drug in vitro, they will also be resistant in vivo to that drug.

Going back years, the article by Schrag et al criticized the field of chemosensitivity and chemo resistance(SRA), concluding that these types of in vitro assays are not yet ready for prime time. The panel of authors attempted to present evidence that in vitro drug response assays should not be used clinically. This issue was first addressed by an exhaustive Medicare Coverage Advisory Committee (MCAC) in 1999. A panel of physicians selected by the Department of Health and Human Services reviewed hundreds of articles from the literature and heard two days of testimony by experts in the field in an open hearing. The panel voted unanimously that although chemosensitivity assays should not be covered, drug resistance assays should be paid for. This became a cause celebre with a vigorous debate in the literature and variant opinions offered by professional bodies. The American Society of Clinical Oncology vigorously objected and recommended: ”
The use of chemotherapy sensitivity and resistance assays to select chemotherapeutic agents for individual patients is not recommended outside of the clinical trial setting. Oncologists should make chemotherapy treatment recommendations on the basis of published reports of clinical trials and a patient’s health status and treatment preferences. Because the in vitro analytic strategy has potential importance, participation in clinical trials evaluating these technologies remains a priority.” I believe that the So. California branch of ASCO dissented from this recommendation, see http://weisenthal.org/medicareletter.pdf.

The Extreme Drug Resistance Assay (EDR) Assay is a laboratory test performed on a patient’s tumor cells. This lab test is claimed to determine the probability of a tumor’s resistance to a specific chemotherapy drug. If the tumor cells grow in the presence of very high concentrations of chemotherapy drug, then the cancer cells are considered resistant to that drug.

Drug sensitivity and resistance assays have been examined for their potential utility in ovarian cancer by a number of clinical investigators. Unfortunately, analysis of these studies has suffered greatly from the absence of an appropriate control population. The majority of these trials have compared the survival of individuals whose treatment was selected by a particular assay with a historical/retrospective patient group treated at the same institution. A report in the Gynecologic Cancer session described an important attempt by investigators in Europe to directly address the value of the adenosine triphosphate (ATP)-based tumor chemosensitivity assay, by randomizing patients with platinum-resistant ovarian cancer (n = 180) to either “assay-directed therapy” or the treatment of the “physician’s choice”. The objective response rate was 40.5% for the assay-directed group vs 31.5% for the physician’s choice of treatment. Progression-free survival (intention-to-treat analysis) was 104 days in the assay-directed vs 93 days in the physician’s choice groups. In addition, there was no difference in overall survival between the strategies. This study provides support for the conclusion that the ATP-based tumor chemosensitivity assay is not superior to physician’s choice in the selection of chemotherapy in women with platinum-resistant ovarian cancer.Some experts claim that resistance assays are different from chemosensitivity assays and Medicare does cover them. However, this distinction has not been sufficiently demonstrated and most experts vigorously dispute this.

In conclusion, the technologies and the questions that they raise are quite different. It Oncotech Sensitivy testing not yet been recommended by professional societies and gudielines pending completion of a phase III trial. With Oncotech ER the situation is more uncertain, NCCN says that “current evidence is not sufficient to supplant standard of care chemotherapy”.

More recently in ASCO 2008, researchers affiliated with Precision Therapeutics and Columbia University reported that a test of chemoresponsiveness (ChemoFX®) can predict survival of patients with advanced ovarian cancer. This remains something that must be confirmed by future studies. NCCN says that “chemosensitivity.resistance assays are being used in some NCCN centers”, which I consider something less than an endorsement. This is a level 3 recommendations, which is defined as: “The recommendation is based on any level of evidence but reflects major disagreement.”

Burstein et al (2011) updated the ASCO Technology Assessment guidelines on CSRAs published in 2004. An Update Working Group reviewed data published between December 1, 2003, and May 31, 2010. Medline and the Cochrane Library were searched yielding 11,313 new articles. The limits for “human and English” were used, and then standard ASCO search strings for randomized controlled trials (RCTs), meta-analyses, guidelines, and reviews were added, yielding 1,298 articles for abstract review. Of these, only 21 articles met pre-defined inclusion criteria and underwent full text review, and 5 reports of RCTs were included for data extraction. Review of the literature does not identify any CSRAs for which the evidence base is sufficient to support use in oncology practice. The authors concluded that the use of CSRAs to select chemotherapeutic agents for individual patients is not recommended outside of the clinical trial setting. They noted that oncologists should make chemotherapy treatment recommendations based on published reports of clinical trials and a patient’s health status and treatment preferences. Because the in vitro analytic strategy has potential importance, participation in clinical trials evaluating these technologies remains a priority.

Schrag D, Garewal HS, Burstein HJ, et al: American Society of Clinical Oncology technology assessment: Chemotherapy sensitivity and resistance assays. J Clin Oncol 22 : 3631 -3638, 2004

John P. Fruehauf In Vitro Drug Resistance Versus Chemosensitivity: Two Sides of Different Coins Journal of Clinical Oncology, Vol 23, No 15 (May 20), 2005: pp. 3641-3643

P. Hwu, A. Y. Bedikian, and E. A. Grimm
Challenges of chemosensitivity testing.
Clin. Cancer Res., September 15, 2006; 12(18): 5258 – 5259.

Cree IA. Chemosensitivity and chemoresistance testing in ovarian cancer. Curr Opin Obstet Gynecol. 2009;21(1):39-43.

C.Rass K, Hassel JC. Chemotherapeutics, chemoresistance and the management of melanoma. G Ital Dermatol Venereol. 2009;144(1):61-78.

Lyons JM 3rd, Abergel J, Thomson JL, et al. In vitro chemoresistance testing in well-differentiated carcinoid tumors. Ann Surg Oncol. 2009;16(3):649-655.

National Comprehensive Cancer Network (NCCN). Ovarian cancer including fallopian tube cancer and primary peritoneal cancer. NCCN Clinical Practice Guidelines in Oncology v.2.2011. Fort Washington, PA: NCCN; 2011.

Burstein HJ, Mangu PB, Somerfield MR, et al. American society of clinical oncology clinical practice guideline update on the use of chemotherapy sensitivity and resistance assays. J Clin Oncol. 2011;29(24):3328-3330.