Cancer Treatment

PET for gastric cancer

Positron emission tomography using 2-deoxy-2-[18F] fluorodeoxyglucose (FDG-PET) has been used to detect malignancies associated with certain kinds of tumors. Data regarding the use of FDG-PET scan for evaluating gastric cancer are scarce. A recent review of studies showed that PET produced an estimated 14% change was noted in management effect, based on 109 patient studies for diagnosis/staging in gastric cancer; however, this is no randomized data.NCCN sys that PET is optional for staging.

Table of studies: http://www.petscaninfo.com/zportal/portals/phys/clinical/jnmpetlit/index_html/JNM_OncoApps/JNM_Table10/article_elements_view

http://www.nccn.org/professionals/physician_gls/PDF/gastric.pdf, p.5

Imaging Gastric Cancer with PET and the Radiotracers 18F-FLT and 18F-FDG: A Comparative Analysis Ken Herrmann, Katja Ott, Andreas K. Buck, Florian Lordick, Dirk Wilhelm, Michael Souvatzoglou, Karen Becker, Tibor Schuster, Hans-Jürgen Wester, Jörg R. Siewert, Markus Schwaiger, and Bernd J. Krause J Nucl Med 48: 1945-1950; First published on November 15, 2007;

Followup of resected gastric cancer

Patients with early gastric cancer have an excellent prognosis after appropriate treatment, with a high survival rate and a low rate of recurrence.There are no guidelines as to how to follow gastric cancer. A recent review concluded: " Early detection of asymptomatic gastric cancer recurrence did not improve overall survival of patients with recurrence after curative resection. Until development of more effective treatment for this disease, close follow-up may offer no survival benefit. " After 5 years, it is usually assumed that a cancer is cured and the proposed intensive re-evalaution in not supported by credible literature.It is still unclear whether intensive follow-up after surgery produces significant benefits in patients with gastric cancer. A previous retrospective study concluded that follow-ups were not useful.There have been no data to suggest that chemotherapeutic agents are useful in the treatment of recurrent gastric cancer detected during follow-up.

C. Kunisaki, H. Akiyama, M. Nomura, G. Matsuda, Y. Otsuka, H. Ono, Y. Nagahori, H. Hosoi, M. Takahashi, F. Kito, et al.
Significance of Long-Term Follow-Up of Early Gastric Cancer
Ann. Surg. Oncol., March 1, 2006; 13(3): 363 - 369.

Yasuhiro Kodera, MD, Seiji Ito, MD, Yoshitaka Yamamura, MD, Yoshinari Mochizuki, MD, Michitaka Fujiwara, MD, Kenji Hibi, MD, Katsuki Ito, MD, Seiji Akiyama, MD and Akimasa Nakao, Follow-Up Surveillance for Recurrence After Curative Gastric Cancer Surgery Lacks Survival Benefit Annals of Surgical Oncology 10:898-902 (2003)

Kodera Y, Ito S, Yamamura Y, et al. A follow-up surveillance for recurrence after curative gastric cancer surgery lacks survival benefit. Ann Surg Oncol 2003; 10:898–902.[

Oxaliplatin and Xeloda combinations for gastric cancer

Epirubicin-cisplatin-5-fluorouracil (ECF) is commonly used to treat advanced gastric cancer. Two new cytotoxic agents: the platinum, oxaliplatin, and the oral fluoropyrimidine, capecitabine, have the potential to replace the cisplatin and 5-fluorouracil (5-FU) components of ECF, respectively. Oxaluplatin combinations are now standard therapy for gastric cancer. Oxaliplatin based therapy is one of the options listed by NCCN for metastatic gastric cancer. The various oxaliplatin regimens in used has been extensively studied in Phase II; there are also studies with capecitabine and exaliplatin. The 5FU.Leukovorin/oxaliplatin combination is approved by Cancer Care of Ontario which has issued evidence based recommendations and a guideline to support it (at http://www.cancercare.on.ca/pdf/pebc2-22s.pdf).            

The aims of palliative treatments for cancer patients are not only centred on efficacy of the treatments but also must be balanced against the potential for toxicity, quality of life and convenience for patients. In the REAL-2 trial presented at ASCO 2006, the central research question was whether capecitabine, an oral pro-drug, could replace protracted venous infusion 5-FU, and whether oxaliplatin could replace cisplatin in the treatment of patients with advanced/non-resectable oesophago-gastric cancers. The use of capecitabine would remove the requirement for central venous access, and the potential line-related complications and morbidity therein. Moreover, oxaliplatin has a different toxicity profile to cisplatin, and is notably less nephro- and oto-toxic.

The REAL-2 study of 1,002 patients with gastrooesophageal cancer had a two-by-two factorial design, comprised four treatment arms with ECF as the reference arm (see Figure 2) and was designed to demonstrate non-inferiority of capecitabine over 5-FU, and oxaliplatin over cisplatin in the perprotocol population. Approximately 40% of patients had gastric cancer. There were no significant differences in quality of life between the arms. In another phase III study of modified FOLFOX6 (FLO) versus infused 5-FU plus cisplatin (FLP), powered to demonstrate superiority of FLO for TTP on an intent-to-treat basis, 220 patients with advanced gastric cancer were randomised with similar results.

Annamaria Ruzzo, Francesco Graziano, Kazuyuki Kawakami, Go Watanabe, Daniele Santini, Vincenzo Catalano, Renato Bisonni, Emanuele Canestrari, Rita Ficarelli, Ettore Tito Menichetti, Davide Mari, Enrica Testa, Rosarita Silva, Bruno Vincenzi, Paolo Giordani, Stefano Cascinu, Lucio Giustini, Giuseppe Tonini, Mauro Magnani  Pharmacogenetic Profiling and Clinical Outcome of Patients With Advanced Gastric Cancer Treated With Palliative Chemotherapy Journal of Clinical Oncology, Vol 24, No 12 (April 20), 2006: pp. 1883-1891

Cunningham D, Rao S, Starling N, et al.,“Randomised multicentre phase III study comparing capecitabine with fluorouracil and oxaliplatin with cisplatin in patients with advanced oesophagogastric (OG) cancer:The REAL 2 trial”, J Clin Oncol 2006 ASCO Annual Meeting Proceedings (2006);24: Abstract LBA4017.

http://www.nccn.org/professionals/physician_gls/PDF/gastric.pdf

J. S. Macdonald Gastric cancer--new therapeutic options.
N. Engl. J. Med., July 6, 2006; 355(1): 76 - 77

M. H. Kulke The Treatment of Advanced Gastric Cancer: In Search of the Right Combination
J. Clin. Oncol., July 14, 2000; 18(14): 2645 - 2647.

C. Louvet, T. Andre, J.M. Tigaud, E. Gamelin, J.Y. Douillard, R. Brunet, E. Francois, J.H. Jacob, D. Levoir, A. Taamma, P. Rougier, E. Cvitkovic, and A. de Gramont Phase II Study of Oxaliplatin, Fluorouracil, and Folinic Acid in Locally Advanced or Metastatic Gastric Cancer Patients
J. Clin. Oncol., December 1, 2002; 20(23): 4543 - 4548

E. Al-Batran, A. Atmaca, S. Hegewisch-Becker, D. Jaeger, S. Hahnfeld, M. J Rummel, G. Seipelt, A. Rost, J. Orth, A. Knuth, and E. Jaeger
Phase II Trial of Biweekly Infusional Fluorouracil, Folinic Acid, and Oxaliplatin in Patients With Advanced Gastric Cancer
J. Clin. Oncol., February 15, 2004; 22(4): 658 - 663. 6

PET scan for GIST

PET is often sued for staging and monitoring of resposne for GIST tumors. A recent consensus statement says: “The panelists agreed that currently available imaging techniques to evaluate GIST include computed tomography (CT), magnetic resonance imaging (MRI) and fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET). "

The journal Applied Radiology (vol. 34, no. 6, 2005), in an article titled 'Role of Positron Emission Tomographic Imaging in Gastrointestinal Stromal Tumors,' cited case studies where PET 'helped in accurate re-staging by indicating the malignant nature of the hepatic and subhepatic masses and excluding pelvic spread.' The article also noted that, 'when compared with CT alone, PET with FDG and PET/CT provided valuable additional information about the extent and metabolic activity of the disease process. … The advantage of PET lies in its ability to differentiate active tumor from a nonviable necrotic tumor mass, malignant from benign tissue, and recurrent tumor from scar tissue.' (2)  Unfortunately, however, there is little support for EPT in GIst beyond case reports and studies.

The NCCN guidelines for soft tissue sarcoma say that  'CT can be ambiguous, but PET is more definitive' in assessing response to therapy and in determining progression. However, soft tissue sarcoma is a different condition than GIST. The aforementioned consensus statement concluded: " Evaluation of FDG uptake using PET scanning is recommended when an early detection of tumor response to imatinib treatment is required, e.g. for consideration of surgery after imatinib cytoreduction in rectal tumors (SOR expert opinion, NCCN level 2A). PET scan may also be useful in case of equivocal images suspected to be metastatic. Aside from these cases, PET scan is not mandatory in all GIST patients after complete resection (SOR expert agreement, NCCN level 2A). "

Thus, while a would approve GIST for stagin, I would not do so for monitoring of therapy response, as in this case, as being medically necessary, unless a surgical decision is pending, which is not reflected in the record.

Consensus meeting for the management of gastrointestinal stromal tumors, Annals of Oncology 2005, Vol. 16, No. 4: 566-578.

Van den Abbeele AD, Badawi RD, Cliche JP et al. 18F-FDG-PET predicts response to imatinib mesylate (Gleevec) in patients with advanced gastrointestinal stromal tumors (GIST). Proc Am Soc Clin Oncol 2002; 21: 403a (Abstr 1610).

Stroobants S, Goeminne J, Seegers M et al. 18FDG-Positron emission tomography for the early prediction of response in advanced soft tissue sarcoma treated with imatinib mesylate (Imatinib). Eur J Cancer 2003; 39: 2012–2020.

Antoch G, Kanja J, Bauer S et al. Comparison of PET, CT, and dual-modality PET/CT imaging for monitoring of imatinib (STI571) therapy in patients with gastrointestinal stromal tumors. J Nucl Med 2004; 45: 357–365.

Choi H, Macapinlac H, Burgess M et al. Correlation of computerized tomography (CT) and proton emission tomography (PET) in patients with metastatic GIST treated at a single institution with imatinib mesylate. Proc Am Soc Clin Oncol 2003; 22: 819.

Decitabine and epigenetic therapy for solid cancers

Lay search: Decitabine is being studies for :epigenetic" therapy of solid cacners.

Genes involved in all aspects of tumor development and growth can become aberrantly methylated in tumor cells, including genes involved in apoptosis and cell cycle regulation. Decitabine, 2´-deoxy-5-azacytidine, can inhibit DNA methyltransferases and reverse epigenetic silencing of aberrantly methylated genes. Nucleoside DNA methyltransferase inhibitors, such as decitabine, have been reported to have antitumor activity, especially against hematologic malignancies. Such demethylating agents have been proposed to reactivate tumor suppressor genes aberrantly methylated in tumor cells, leading to inhibition of tumor growth.

Currenlty Decitabine is FDA approved for myedlodysplaisa. Because of the aforementioned emchanism of action, there is interest in studying it in colorectal and oterh solid cancers. Decitabine has been studied in several phase II trials for solid tumours as well as in different types of leukaemia. The drug has been shown to have very limited efficacy against solid tumours. However, decitabine exhibits higher activity for the treatment of haematological malignancies.

Robert Brown, Jane A Plumb Demethylation of DNA by decitabine in cancer chemotherapyExpert Review of Anticancer Therapy August 2004, Vol. 4, No. 4, Pages 501-510

Saba H, Rosenfeld C, Issa JP, et al. First Report of the Phase III North American Trial of Decitabine in Advanced Myelodysplastic Syndrome. American Society of Hematology Meeting. San Diego, Calif. 2004. Abstract #64.

Kantarjian H, O'Brien S, Giles F, et al.Decitabine Low-Dose Schedule (100 mg/m2/Course) in Myelodysplastic Syndrome (MDS). Comparison of 3 Different Dose Schedules.American Society of Hematology Meeting. Atlanta, Georgia. 2005. Abstract #2522.

http://jco.ascopubs.org/cgi/reprint/JCO.2004.01.947v1.pdf

Adis Decitabine: 2'-Deoxy-5-azacytidine, Aza dC, DAC, Dezocitidine, NSC 127716. R&D Profile Drugs in R & D. 4(6):352-358, 2003.

Jean-Pierre J. Issa DNA Methylation as a Therapeutic Target in Cancer Clinical Cancer Research 13, 1634-1637, March 15, 2007.

Neoadjuvant chemotherapy for resectable gastric cancer.

Lay Summary: Questions remain about pre-surgery chemo and radiation in stomach cancer that can be resected without these treatments.

The practice of administering chemotherapy before surgery is referred to as neoadjuvant therapy. In theory, neoadjuvant chemotherapy can decrease the size of the cancer, thereby making it easier to remove with surgery. The major problems with this approach are the higher mortality rates that occur when radiation therapy and/or chemotherapy are administered before surgery and the delay of surgery for some patients who do not respond to therapy. In most but not all studies chemotherapy, radiation therapy or both given before surgery have not improved survival following surgery in patients with stage III gastric cancer. This may be related to the ineffectiveness of the drug combinations tested, which include various combination of 5-FU, doxorubicin and methotrexate. Many current clinical trials are directed at improving outcomes of patients with stage III gastric cancer by administering newer neoadjuvant treatment regimens containing taxane chemotherapy and/or radiation therapy.

There is insufficient evidence from randomized trials to recommend neoadjuvant chemotherapy, or neoadjuvant or adjuvant radiation therapy or immunotherapy, either alone or in combination, outside of a clinical trial

Gastrointestinal Cancer Disease Site Group. Earle CC, Maroun J, Zuraw L. Neoadjuvant or adjuvant therapy for resectable gastric cancer [full report]. Toronto (ON): Cancer Care Ontario (CCO); 2003 May 21 [online update]. 21 p. (Practice guideline; no. 2-14). [79 references]
nccn.org, stomach cancer.

Alimta for gastric cancer

Lay Summary: Activity of Alimta for gastric cancer is supported by phase II studies.

Gastric (stomach) cancer is the 14th most common cancer in the United States. Approximately 90% of gastric cancers are classified as adenocarcinomas, in reference to the type of cell within the stomach that the cancer originated. The main component of treatment for patients who cannot have their cancer surgically removed due to extent of spread and/or location of the cancer is chemotherapy. There are several standard chemotherapy regimens for advanced gastric cancer, all achieving approximately a 20% anti-cancer response rate and overall survivals of 6-7 months. Researchers from Italy conducted a clinical trial in 2003 to evaluate the chemotherapy agent Alimta® in the treatment of advanced gastric cancer. This trial involved 38 patients with advanced (stage IV) gastric cancer who were treated with Alimta®. Anti-cancer responses occurred in 21% of patients, with 2 patients achieving a complete disappearance of detectable cancer and 6 patients achieving a partial disappearance of cancer. Overall survival for this group of patients was 7.8 months. Side effects included low levels of blood cells.

Another single agent ALimta study was performed in Korea and can be seen at http://www.lillytrials.com/results_files/alimta/alimta_summary_6154.pdf

Oncotech chemosensitivity and chemoresistance assays

Lay Summary: 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.

Oncotech ER is a form of chemosensitivity testing, or rather, a modification that tests resistance to chemo rather than sensitivity. The recent article by Schrag et al1 criticized the field of chemosensitivity and drug resistance, 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 casue celebre with a vigorous debate in the literature and variant opinions offered by professional bodies. The Amreican Society of Clnical 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 disssented 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 expersts 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 as described above.

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.

M. Markman Chemosensitivity and Chemoresistance Testing
J. Clin. Oncol., October 10, 2005; 23(29): 7363 - 7364.

R. Nagourney Chemosensitivity and Resistance Assays: A Systematic Review?
J. Clin. Oncol., May 20, 2005; 23(15): 3640 - 3641.

J. P. Fruehauf and D. S. Alberts
In Vitro Drug Resistance Versus Chemosensitivity: Two Sides of Different Coins
J. Clin. Oncol., May 20, 2005; 23(15): 3641 - 3643.
 
H. S. Wieand
Chemotherapy Sensitivity and Response Assays: Are the ASCO Guidelines for Clinical Trial Design Too Restrictive?
J. Clin. Oncol., May 20, 2005; 23(15): 3643 - 3644.
 
M. Castro Resisting a Fundamentalist Policy
J. Clin. Oncol., May 20, 2005; 23(15): 3645 - 3646.

Oxali/5FU/LV for gastric cancer

Lay Summary: Oxaluplatin combinations are standard therapy for gastric cancer.

Oxaliplatin based therapy is one of the options listed by NCCN for metastatic gastric cancer. The particular regimens that is being used has been extensively studies in Phase II; there are also studies of capecitabine and exaliplatin. This combination is approved by Cancer Care of Ontario which has issued evidence based recommendations and a guideline to support it (at http://www.cancercare.on.ca/pdf/pebc2-22s.pdf).            

Rationale:

Annamaria Ruzzo, Francesco Graziano, Kazuyuki Kawakami, Go Watanabe, Daniele Santini, Vincenzo Catalano, Renato Bisonni, Emanuele Canestrari, Rita Ficarelli, Ettore Tito Menichetti, Davide Mari, Enrica Testa, Rosarita Silva, Bruno Vincenzi, Paolo Giordani, Stefano Cascinu, Lucio Giustini, Giuseppe Tonini, Mauro Magnani  Pharmacogenetic Profiling and Clinical Outcome of Patients With Advanced Gastric Cancer Treated With Palliative Chemotherapy Journal of Clinical Oncology, Vol 24, No 12 (April 20), 2006: pp. 1883-1891

http://www.nccn.org/professionals/physician_gls/PDF/gastric.pdf

J. S. Macdonald Gastric cancer--new therapeutic options.
N. Engl. J. Med., July 6, 2006; 355(1): 76 - 77

M. H. Kulke The Treatment of Advanced Gastric Cancer: In Search of the Right Combination
J. Clin. Oncol., July 14, 2000; 18(14): 2645 - 2647.

C. Louvet, T. Andre, J.M. Tigaud, E. Gamelin, J.Y. Douillard, R. Brunet, E. Francois, J.H. Jacob, D. Levoir, A. Taamma, P. Rougier, E. Cvitkovic, and A. de Gramont Phase II Study of Oxaliplatin, Fluorouracil, and Folinic Acid in Locally Advanced or Metastatic Gastric Cancer Patients
J. Clin. Oncol., December 1, 2002; 20(23): 4543 - 4548

E. Al-Batran, A. Atmaca, S. Hegewisch-Becker, D. Jaeger, S. Hahnfeld, M. J Rummel, G. Seipelt, A. Rost, J. Orth, A. Knuth, and E. Jaeger
Phase II Trial of Biweekly Infusional Fluorouracil, Folinic Acid, and Oxaliplatin in Patients With Advanced Gastric Cancer
J. Clin. Oncol., February 15, 2004; 22(4): 658 - 663. 6

DCF in gastric cancer

Most cases of stage IV gastric cancer cannot be curatively treated with surgery alone, except for those with N3 or T4N2 cancers. Chemotherapy is therefore essentially palliative.
There is no evidence of survival benefit for treatment modalities other than surgery for stage IV cancer, but some benefits are suggested for marginal life prolongation, tumor shrinkage, and relief of symptoms.

Chemotherapy is indicated for patients with unresectable tumor with good performance status. Standard regimens of chemotherapy for late stage cancer are not yet established, although combination chemotherapy with cisplatin (CDDP), and 5 fluorouracil ( 5FU) or its derivates may be the regimen of preference and recommendation. A number of controlled studies of two-drug combination chemotherapies, especially cisplatin-containing regimens, have shown a significant improvement in median survival and quality of life compared with best supportive care. Of these, 5-FU and cisplatin combination (FP) has been considered an active and safe regimen for a long time. More recently drugs such as paclitaxel, docetaxel, oxaliplatin and irinotecan have been added in various trials. 
Many trials using combinations of three drugs have been conducted to improve treatment results further in advanced gastric cancer. One of the three-drug combination is adding docetaxel, a novel semi-synthetic taxoid, to ‘5-FU + cisplatin’ (DCF). According to the interim analysis of a recent randomized phase III study by Ajani et al., the DCF regimen is superior to the FP regimen in terms of response rate, time to progression and overall survival with manageable toxicity as a first-line treatment in advanced gastric cancer. However, the superiority of three-drug combinations to two-drug combinations has not been accepted worldwide yet.

Romeo Giuli, Gastric Cancer Treatment Guidelines in Japan. Journal of Surgical Oncology, August 2002 (http://www.geocities.com/surgoncnet/guidelines2.htmMD)

Ajani J, Bekaii-Saab T, D'Amico TA, Fuchs C, Gibson MK, Goldberg M, Hayman JA, Ilson DH, Javle M, Kelley S, Kurtz RC, Locker GY, Meropol NJ, Minsky BD, Orringer MB, Osarogiagbon RU, Posey JA, Roth J, Sasson AR, Swisher SG, Wood DE, Yen Gastric Cancer Clinical Practice Guidelines.J Natl Compr Canc Netw. 2006 Apr;4(4):350-66.

Tobias Götzea et al, Recent Developments in Chemotherapy of Advanced Gastric Cancer, Digestive Diseases Vol. 22, No. 4, 2004   

D.-Y. Oh, T.-Y. Kim, J. H. Kwon, J.-J. Lee, Y. Joh, D.-W. Kim, T.-Y. Kim, D. S. Heo, Y.-J. Bang, and N. K. Kim
Docetaxel + 5-Fluorouracil + Cisplatin 3-day Combination Chemotherapy as a First-line Treatment in Patients with Unresectable Gastric Cancer
Jpn. J. Clin. Oncol., July 1, 2005; 35(7): 380 - 385.

Ajani JA, Van Cutsem E, Moiseyenko V, Yjulandin S, Fodor M, et al. Docetaxel, cisplatin, 5-fluorouracil compared to cisplatin and 5-fluorouracil for chemotherapy-naïve patients with metastatic or locally recurrent, unresectable gastric carcinoma: interim results of a randomized phase III trial (V325). Proc Am Soc Clin Oncol 2003;22:249 (abstr 999).