???: ????

1
????? ?????? ????? ?????? ?????

• ????? ????, ????? ????? ??????? ??????
• ??? ???? 2000
• ??? ???? ?. ???? , ??? 2004 , ????? ??????
  2006
• ????? ???? ???????
• ????? ?????? ??????
• n_haim_at_rambam.health.gov.il

2

• CTCAE formerly known as CTC (CommonToxicity
  Criteria)..

3
CTCAE formerly known as CTC (Common Toxicity
Criteria Common Toxicity Criteria)

• http//ctep.cancer.gov
• ..CTCAE (formerly known as CTC) v2.0 and
  v3.0
• (v3.0 publish date December 12, 2003)

4
Chemotherapy-induced nausea and vomiting

• Recent guidelines.
• NK1 receptor antagonists.
• ??? ???? "??????? ????? ??????? ?? ??????
  ??????????? ??????? ?????? ???? ?????? ????? ??
  ??????? ??????.

5
Chemotherapy-induced nausea and vomiting-Recent
guidelines

• 1. Perugia International Cancer Conference VII-
  MASCC (Multinational Association of Supportive
  Care in Cancer)
• www.mascc.org (last update Sept 2005)
• See also The Antiemetic Subcommittee of the
  Multinational Association of the Multinational
  Association of Supportive Care in Cancer (MASCC).
  Ann Oncol 17 20-8, 2006.
• 2. ASCO Guidelines
• Kris MG et al. J Clin Oncol 24 May 22, 2006
  (published ahead of print)
• 3. National Comprehensive Cancer Network (NCCN)
• http//www.nccn.com ---see Clinical
  Practice Guidelines in Oncology-v.2.2006----see
  Antiemesis

6
NK1 receptor antagonists

• de Wit R et al. Addition of the oral NK1
  antagonist Aprepitant to standard antiemetics
  provided protection against nausea and vomiting
  during multiple cycles of cispltin-based
  chemotherapy. J Clin Oncol 21 4105-11, 2003
• Hesketh PJ et al. The oral neurokinin-1
  antagonist Aprepitant for the prevention of
  chemotherapy-induced nausea and vomiting a
  multinational , randomized , double-blind,
  placebo-controlled trial in patients receiving
  high-dose cisplatin-the Aprepitant Protocol 052
  Study Group. J Clin Oncol 21 4112-19, 2003
• Kris MG. Why do we need another antiemetic? Just
  ask. J Clin Oncol 21 4077-80, 2003 (editorial)

7
Chemotherapy and radiotherapy protectants

• ASCO guidelines for the use of mesna,
  dexrazoxane,and amifostine .
• ??? ???? "??????? ????? ??????? ?? ??????
  ??????????? ??????? ?????? ???? ?????? ????? ??
  ??????? ??????....
• ??? ???? "???????????? ?????????..." ???? ?????
  ??? ?? mesna.
• ??? ?? ?????? ???? ?????????? ????? ???? ??????
  ???????? ?? ?????????? ??????? ?"? ????????? ?
• www.iscort.org.il

8
Chemotherapy and radiotherapy protectants-ASCO
Guidelines

• Schuchter LM et al. 2002 update of
  recommendations for the use of chemotherapy and
  radiotherapy protectants clinical practice
  guidelines of the American Society of Clinical
  Oncology. J Clin Oncol 20 2895-2903, 2002
• Guidelines for the use of mesna, dexrazoxane,
  and amifostine.

9
ASCO recommendations on fertility preservation in
cancer patients
10
ASCO recommendations on fertility preservation in
cancer patients

• Lee SJ et al. J Clin Oncol 24 2917-31, 2006

11
GCSF Feblile neutropenia

• NCCN Guidelines.
• ASCO Guidelines (GCSF).
• EORTC Guidelines.
• 2002 guidelines of the Infectious Diseases
  Society of America (IDSA) Fever and Neutropenia
  Guidelines Panel.
• Antibacterial prophylaxis after chemotherapy for
  solid tumors and lymphomas.
• ??? ?? ???? "??????? ????? ?? ?????? ???????????
  ??????? ??????"
• ??? ?? ?????? ???? ?????????? ?????? ??????
  ????? ?? ????? ????? ?
• www.iscort.org.il

12
GCSF- NCCN, ASCO EORTC Guidelines

• NCCN Clinical Practice Guidelines in Oncology /
  Myeloid Growth Factors in Cancer Treatment /
  Version 2.2005
• http//www.nccn.com
• ASCO 2006 Update of recommendations for the use
  of white blood cell growth factors an
  evidence-based, clinical practice guidelines.
  Smith TJ et al. for the American Society of
  Clinical Oncology Growth Factor Expert Panel.
  Published ahead of print on J Clin Oncol May 8,
  2006
• EORTC EORTC guidelines for the use of
  granulocyte-colony stimulating factor to reduce
  the incidence of chemotherapy-induced febrile
  neutropenia adult patients with lymphomas and
  solid tumors. Aapro MS et al. Published ahead of
  print, Europ J Cancer , 2006

13
2002 guidelines of the Infectious Diseases
Society of America (IDSA) Fever and Neutropenia
Guidelines Panel

• Hughes WT et al. Clin Infect Dis 34 730-51, 2002

14
Antibacterial prophylaxis after chemotherapy for
solid tumors and lymphomas

• Cullen M et al. N Engl J Med 353 988-98, 2005
• Pts treated with chemo protocols associated
  with severe neutropenia, but not routinely
  treated with GCSF, were randomized to receive
  levofloxacin or placebo for 7 days to cover the
  the period of anticipated neutropenia.
• The prophylactic use of levofloxacin reduced
  the incidence of fever, probable infection, and
  hospitalization.

15
Epoeitin

• ASCO/ASH Guidelines.
• EORTC Guidelins.

16
Epoeitin-ASCO EORTC Guidelines

• Rizzo JD et al. Use of Epoeitin in patients with
  cancer evidence-based clinical practice
  guidelines of the American Society of Clinical
  Oncology and the American Society of Hematology.
  J Clin Oncol 20 4083-4107, 2002
• Guidelines for the use of epoietin in patients
  with chemotherapy induced anemia.
• Bokemeyer C et al. EORTC guidelines for the use
  of erythropoietic proteins in anemic patients
  with cancer. Eur J Cancer 40 2201-16, 2004
• Guidelines for the use of epoietin in anemic
  cancer patients.

17
Recommended guidelines for the treatment of
cancer chemotherapy-induced diarrhea

• Independent panel (mortality associated with
  IFL)
• Panel recommendations.
• ??? ?? ?????? ???? ?????????? ?????? ??????
  ?????? ??????????-?? ??? ???? ?????????? ?
• www.iscort.org.il

18
Independent panel-mortality associated with IFL

• Rothenberg ML et al. Mortality associated with
  irinotecan plus bolus fluorouracil/leucovorin
  summary findings of an independent panel. J Clin
  Oncol 19 3801-7, 2001
• Guidelines suggested after a report of high
  mortality rate associated with the Saltz
  regimen.

19
Recommended guidelines for the treatment of
cancer chemotherapy-induced diarrhea

• Benson III Al B et al. Recommended guidelines for
  the treatment of cancer treatment-induced
  diarrhea. J Clin Oncol 22 2918-26, 2004
• Guidelines of an independent panel of
  experts. Includes also guidelines for
  radiotherapy-induced diarrhea).
• See also previous panel recommendations
  (Wadler S et al. Recommended guidelines for the
  treatment of chemotherapy-induced diarrhea. J
  Clin Oncol 16 3169-3178, 1998)

20
Extravasation of cytotoxic agents

• ??? ?? ?????? ???? ?????????? ?????? ??????
  ?????? ???? ?????? ?? ?????? ??????????? ?
• www.iscort.org.il

21
Extravasation of cytotoxic agents

• Ener RA et al. Extravasation of systemic
  hemato-oncological therapies. Ann Oncol 15
  858-62, 2004
• includes background and suggested guidelines.

22
Chemotherapy sensitivity and resistance assays

• ASCO assessment.

23
Chemotherapy sensitivity and resistance assays
ASCO assessment

• Schrag D et al. American Society of Clinical
  Oncology technology assessment chemotherapy
  sensitivity and resistance assays. J Clin Oncol
  22 3631-8, 2004
• The use of chemotherapy sensitivity and
  resistance assays to select chemotherapeutic
  agents for individual patients is not recommended
  outside the clinical trial setting.
• See also a systematic review
• Samson DJ et al. J Clin Oncol 22 3618-30,
  2004
• .These results do not establish the
  relative effectiveness of assay-guided treatment
  and empiric treatment.

24
Thalidomide

• Mechanism of action, side effects, current role
  in solid tumors.

25
Thalidomide Mechanism of action, side effects,
current role in solid tumors

• Kumar S et al. J Clin Oncol 22 2477-88, 2004
  (review) and/or Eleutherakis-Papaiakovou V et
  al. Ann Oncol 15 1151-60, 2004 (review)

26
Somatostatin analogs

• Consensus report of the use of somatostatin
  analogs for the management of neuroendocrine
  tumors of the gastroenteropancreatic system.

27
Somatostatin analogs

• Oberg K et al. Consensus report of the use of
  somatostatin analogs for the management of
  neuroendocrine tumors of the gastroenteropancreati
  c system. Ann Oncol 15 966-73, 2004
• A consensus report on the use of somatostatin
  analogs in the management of neuroendocrine
  tumors of the gastroenteropancreatic system.

28
Bisphosphonates

• ASCO Guidelines.

29
Bisphosphonates-ASCO Guidelines

• Hillner BE et al. American Society of Clinical
  Oncology 2003 Update on the Role of
  Bisphosphonates and Bone Health Issues in Women
  With Breast Cancer. J Clin Oncol 21 4042-57,
  2003
• Schedule of administration of pamidronate,
  and zoledronic acid guidelines for
  administration in patients with renal
  dysfunction.
• see also previous version J Clin Oncol 18
  1378-91, 2000.

30
Brain Tumors

• Radiotherapy plus concomitant and adjuvant
  temozolomide for glioblastoma.

31
Radiotherapy plus concomitant and adjuvant
temozolomide for glioblastoma

• Stupp R et al. N Engl J Med 352 987-96, 2005
• The addition of temozolomide to radiotherapy
  for newly diagnosed glioblastoma resulted in
  clinically meaningful and statistically
  significant survival benefit with minimal
  additional toxicity.

32
Breast cancer

• Dose-dense vs. conventional AC/taxol as adjuvant
  in node-positive breast cancer.
• Adjuvant docetaxel for node-positive breast
  cancer (TAC vs. FAC).
• ATAC.
• Letrozole vs tamoxifen as adjuvant..
• adjuvant hormone therapy beyond tamoxifen
• - Exemestane after 2 to 3 years of tamoxifen in
• post menopausal women.
• - Anastrazole after 2-3 yrs of tamoxifen.
• - Letrozole after 5 years of tamoxifen.
• Herceptin with chemotherpy and as single agent
  ..
• Herceptin every 3 weeks.
• Herceptin as adjuvant.
• HER2 and responsiveness of breast cancer to
  adjuvant chemo.
• ASCO technology assessment of the use of
  aromatase inhibitors.

33
Dose-dense vs. conventional AC/taxol as adjuvant
in node-positive breast cancer

• Citron ML et al. J Clin Oncol 21 1431-39, 2003
• See also editorial Piccart-Gebhart MJ,
  Mathematics and oncology a mach for life? J Clin
  Oncol 21 1425-8, 2003 (editorial)
• The dose-dense arms improved DFS severe
  neutropenia was less frequent in pts treated with
  the dose-dense regimens.

34
Adjuvant docetaxel for node-positive breast
cancer (TAC vs. FAC)

• Martin M et al. N Engl J Med 352 2302-13, 2005
• Adjuvant chemo with TAC, as compared with
  FAC, significantly improves the rates of
  disease-free and overall survival among women
  with operable node-positive breast cancer.

35
ATAC study

• Atac Trialists Group. Results of the ATAC
  (arimidex, tamoxifen, alone or in combination)
  trial after completion of 5 years adjuvant
  treatment for breast cancer. Lancet December 8,
  2004

36
Breast cancer-Extending adjuvant hormone therapy
beyond tamoxifen

• Goss PE et al. N Engl J Med 349 1793-802, 2003
• As compared with placebo, letrozole after the
  completion of standard tamoxifen significantly
  improves DFS. (See also updated report Goss PE
  et al. J Natl Cancer Inst 97 1262-71, 2005)
• Coombes RC et al. N Engl J Med 350 1081-92, 2004
• Exemestane therapy after 2 to 3 years of
  tamoxifen significantly improved DFS as compared
  with the standard 5 yrs of tamoxifen.
• Boccardo F et al. J Clin Oncol 22 5138-47, 2005
• Anastrazole after 2 to 3 years of tamoxifen
  significantly improved DFS as compared with the
  standard 5 yrs of tamoxifen (see also editorial
  Pritchard KI. J Clin Oncol 22 4850-2, 2005)

37
Letrozole vs tamoxifen as adjuvant

• The Breast International Group (big) I-98 Group.
  N Engl J Med 353 2747-57, 2005
• Compared with tamoxifen, letrozole reduced
  the risk of recurrent disease, especially at
  distant sites.

38
Herceptin chemotherpy and as single agent

• Slamon DJ et al. N Engl J Med 344 783-792, 2001
• Herceptin increases the clinical benefit of
  first-line chemotherapy in MBC that overexpress
  HER 2.
• Vogel CL et al. J Clin Oncol 20 719-26, 2002
• Single agent herceptin is active and well
  tolerated (objective response rate 26 34 in
  FISH positive).

39
Herceptin every 3 weeks

• Leyland-Jones B et al. J Clin Oncol 21 3965-71,
  2003
• Herceptin every 3 weeks in combination with
  paclitaxel is generally well tolerated.
  Additional investigation of this schedule is
  warranted.
• See also editorial
• Cobleigh M and Frame D. J Clin Oncol 21 3900-1,
  2003

40
Herceptin as adjuvant therapy- randomized trials

• Piccart-Gebhart M et al. N Engl J Med 353
  1659-72, 2005 (HERA herceptin adjuvant)
• (Herceptin every 3 wks was given for one or
  two years after locoregional therapy).
• Romond EH et al. N Engl J Med 353 1673-84, 2005
  (NSABP B-31 Intergoup N9831)
• Herceptin weekly for one year initiated after
  AC paclitaxel adjuvant therapy or concomitantly
  with paclitaxel).
• Joensuu H et al. N Engl J Med 354 809-20, 2006
  (FinHerFinish trial)
• Herceptin was given for 9 weeks in
  combination with docetaxel or vinorelbine.

41
HER2 and responsiveness of breast cancer to
adjuvant chemotherapy

• Pritchard KI et al. N Engl J Med 354 2103-11,
  2006
• Amplification of HER2 in breast-cancer cells
  is associated with a larger benefit from CEF
  (cyclophosphamide, epirubicin, 5FU), as compared
  with CMF.

42
ASCO technology assessment of the use of
aromatase inhibitors

• Winer EP, Hudis C, Burstein HJ et al. American
  Society of Clinical Oncology technology
  assessment of the use of aromatase inhibitors as
  adjuvant therapy for postmenopausal women with
  hormone receptor-positive breast cancer status
  report 2004. J Clin Oncol 23 619-29, 2005

43
Colorectal cancer

• Bevacizumab (avastin) in metastatic colorectal
  cancer.
• Oxaliplatin, fluorouracil, and leucovorin as
  adjuvant treatment for colon cancer.
• Cetuximab Cetuximab plus irinotecan in
  irinotecan-refractory MCRC.
• ASCO recommendations on adjuvant chemotherapy for
  stage II colon cancer.
• Capecitabine as adjuvant in stage III (X-ACT).
• Chemotherapy with preoperative radiotherapy in
  rectal cancer.

44
Bevacizumab (avastin) in metastatic colorectal
cancer

• Kabbinavar F et al. J Clin Oncol 21 60-5, 2003
• A phase II randomized study that compared
  5FU/LCV to 5FU/LCV avastin as first-line in
  MCRC. ...encouraging results
• Hurwitz H et al. N Engl J Med 350 2335-42, 2004
• Addition of avastin to standard IFL
  (irinotecan, 5FU, leucovorin) in MCRC improved
  response rate, progression free survival, and
  survival.
• Kabbinavar FF et al. J Clin Oncol 23 June 1,
  2005
• The addition of bevacituzumab to FU/LV
  provides a statistically significant and
  clinically relevant benefit in pts with
  previously untreated CRC.

45
Oxaliplatin, fluorouracil, and leucovorin as
adjuvant treatment for colon cancer

• Andre T et al. N Engl J Med 350 2343-51, 2004
  (Multicenter International Study of
  Oxaliplatin/5-Fluorouracil/Leucovorin in the
  Adjuvant Treatment of Colon CancerMOSAIC)
• Adding oxaliplatin to a regimen of 5FU/LCV
  improves the adjuvant treatment of colon cancer.

46
Cetuximab Cetuximab plus irinotecan in
irinotecan-refractory MCRC

• Cunnigham D et al. N Engl J Med 351337-45, 2004
• Cetuximab has clinically significant activity
  when given alone or in combination with
  irinotecan in pts with irinotecan-refractory CRC.

47
ASCO recommendations on adjuvant chemotherapy for
stage II colon cancer

• Benson III AlB et al. J Clin Oncol 22 3408-19,
  2004

48
Capecitabine as adjuvant in stage III (X-ACT)

• Twelves C et al. N Engl J Med 352 2696-2704,
  2005
• Capecitabine is at least equivalent to the
  Mayo Clinic regimen (better DFS less toxicity.

49
Chemotherapy with preoperative radiotherapy in
rectal cancer

• Bosset JF et al. N Engl J Med 355 1114-23, 2006
• In pts with rectal cancer who receive
  preoperative radiotherapy, adding
  fluorouracil-based chemopre or post operatively
  has no significant effect on survival.
  Chemotherapy (whether pre or post op.) confers a
  significant benefit with respect to local control.

50
Gastric cancer

• Chemoraio after surgery vs surgery alone
  (Macdonald JS et al, NEJM,2001).
• Perioperative chemo (ECF) vs. surgery alone in
  resectable gastrointestinal cancer (MAGIC).

51
Chemo-raiotherapy after surgery vs surgery alone.

• Macdonald JS et al. N Engl J Med 345 725-30,
  2001
• Postoperative chemo (5FU/LCV) and radio
  improves overall survival in high-risk pts with
  adenocarcinoma of the stomach or GEJ.

52
Perioperative chemo (ECF) vs. surgery alone in
resectable gastrointestinal cancer

• Cunningham D et al. N Engl J Med 355 11-20, 2006
  (MAGIC Medical Research Council Adjuvant Gastric
  Infusional Chemotherapy)
• In pts with operable gastric or lower third
  of the esophagus, a prioperative chemo ECF
  epirubicin, cisplatin, and 5FU (continuous
  infusion for 21 days decreased tumor size and
  stage and significantly improved PFS and overall
  survival.

53
Germ cell tumors

• Radiotherapy vs single-dose carboplatin in
  adjuvant treatment of stage I seminoma.

54
Radiotherapy vs single-dose carboplatin in
adjuvant treatment of stage I seminoma

• Oliver RT et al. Lancet 366 293-300, 2005
• A randomized study that showed non-inferiority
  of carboplatin to radiotherapy in the treatment
  of stage I seminoma.

55
Imatinib (Glivec) in GISTs

• .

56
Imatinib (Glivec) in GISTs

• Demetri GD et al. N Engl J Med 347 472-80, 2002
• 54 had PR and 28 had stable disease..no
  significant differences in response rate between
  400 mg/day and 600 mg/day.
• Verweij J et al. Lancet 25 1127-34, 2004
• 5 CR, 47 PR, 32 Stable disease.
• 400 mg/day was similar to 800 mg/day in terms
  of response rate, but the higher dose produced
  significantly longer progression-free survival.

57
Gynecological tumors

• Randomized Intergroup trial of cisplatin-paclitaxe
  l vs. cisplatin-cyclophosphamide in advanced
  epithelial ovarian cancer.

58
Randomized Intergroup trial of cisplatin-paclitaxe
l vs. cisplatin-cyclophosphamide in advanced
epithelial ovarian cancer

• Piccart MJ et al. Randomized trial of
  cisplatin-paclitaxel versus cisplatin-cyclophospha
  mide in women with advanced epithelial ovarian
  cancer three-year results. J Natl Cancer Inst
  92 699-708, 2000
• The paclitaxel-containing combination was
  associated with better progression free survival
  and survival.
• see also GOG study
• McGuire WP et al. N Engl J Med 334 1-6, 1996

59
Head Neck carcinoma

• Post operative irradiation with or without
  concomitant cisplatin for locally advanced
  disease.
• Radiotherapy plus cetuximab vs. radiotherapy
  alone in the treatment of locoregional squamous
  cell carcinoma of H N.

60
Post operative irradiation with or without
concomitant cisplatin for locally advanced disease

• Cooper JS et al. Postoperative concurrent
  radiotherapy and chemotherapy for high-risk
  squamous-cell carcinoma of the head and neck. N
  Engl J Med 350 1937-44, 2004
• Bernier J et al. Postoperative irradiation with
  or without concomitant chemotherapy for locally
  advanced head and neck cancer. N Engl J Med 350
  1952-42, 2004
• Post operative irradiation with concomitant
  cisplatin for locally advanced disease is
  associated with improved local control and
  disease-free survival.

61
Radiotherapy plus cetuximab vs. radiotherapy
alone in the treatment of locoregional squamous
cell carcinoma of H N

• Bonner JA et al. N Engl J Med 354 567-78, 2006
• Combined therapy improves locoregional
  control and reduces mortality without increasing
  the common toxic effects associated with
  radiotherapy to the head and neck.

62
Lung

• Positive phase III trials with cisplatin-based
  adjuvant chemotherapy in pts with completely
  resected NSCLC.
• Gefetinib (Iressa) plus chemotherapy is not
  better than chemotherapy alone.
• Gefitinib/ISEL.
• Erlotinib (Tarceva) in previously treated NSCLC.
• Meta-analysis of cis-containing vs.
  carbo-containing in advanced NSCLC.
• Pemetrexed (Alimta) cisplatin vs.cisplati in
  mesothelioma....

63
Cisplatin-based adjuvant chemotherapy in pts with
completely resected NSCLC

• IALT The International Adjuvant Lung Cancer
  Trial Collaborative Group. N Engl J Med
  350351-60, 2004
• 4 cycles of cisplatin-based chemo
  (vindesine/vinblastine/vinorelbine/etoposide)-imp
  roves survival (stage I-III, who had undergone
  complete resection).
• CALGB Strauss GM et al. J Clin Oncol 22
  621s, abst 7019, 2004
• 4 cycles of cis taxol
• JBR.10 Winton T et al. n Engl J Med 352
  2589-97, 2005 (NCI of Canada NCI of the US)
• 4 cycles of vinorelbine cisplatin prolonged
  DFS and survival in pts with stage IB or II.
• ANITA Douillard J et al. J Clin Oncol 23
  624s, abstr 7013, 2005
• 4 cycles of vinorelbine cisplatin

64
Gefetinib (Iressa) plus chemotherapy is not
better than chemotherapy alone

• (Giaccone G et al. J Clin Oncol 22 777-84, 2004)
• INTACT 1 addition of gefitinib to
  cisplatin/gemcitabine did not improve therapeutic
  outcome in advanced NSCLC
• (Herbst RS et al. J Clin Oncol 22 785-94, 2004)
• INTACT 2 addition of gefitinib to
  paclitaxel/carboplatin did not improve
  therapeutic outcome in advanced NSCLC
• Baselga J. J Clin Oncol 22 759-61, 2004
  (editorial)

65
ISEL study in NSCLC

• A double blind, placebo controlled, parallel
  group, multicenter, randomized, phase III
  survival study, comparing gefitinib (iressa) 250
  mg BSC to BSC in pts with advanced NSCLC who
  have received 1 or 2 prior chemotherapy regimens
  and who are refractory or intolerant to their
  recent regimen.
• Gefitinib failed to improve survival.
• AstraZeneca 17 December 2004 (yet unpublished)

66
Erlotinib (Tarceva) in previously treated NSCLC

• Shepherd FA et al. N Engl J Med 353 123-32,
  2005
• A randomized phase III trial. Erlotinib (100
  mg/day), compared to placebo, can prolong
  survival and decrease symptoms in pts with NSCLC
  after first-line or second-line chemotherapy.

67
Meta-analysis of cis-containing vs.
carbo-containing in advanced NSCLC.

• Hotta K et al. J Clin Oncol 22 3852-9, 2004
• 8 trials (2948 pts) were identified.
• The combination of chemotherapy consisting of
  cisplatin a new agent produced a significant
  survival advantage compared to that of
  carboplatin the same new agent
• There was no advantage to the cisplating-containin
  g chemotherapy in an overall analysis, that
  included both new agents and new agents.

68
Pemetrexed (Alimta) cisplatin vs.cisplati in
mesothelioma

• Vogelzang NJ, Rusthoven JJ, Symanowski J et al.
  Phase III study of pemetrexed in combination with
  cisplatin versus cisplatin alone in patients with
  malignant pleural mesothelioma. J Clin Oncol 21
  2636-44, 2003
• The combination was superior in terms of
  survival, TTP, and response rate.

69
Lymphomas

• CHOP plus rituximab in elderly pts with diffuse
  large-B-cell lymphoma.in young pts with
  good-prognosis in follicular lymphoma
• Intensive chemotherapy (ACVBP) vs. 3 cycles of
  CHOP radiotherapy in localized stage I/II
  aggressive NHL in pts lt 61 yrs without adverse
  prognostic factors.

70
CHOP plus rituximab (Mabthera) in elderly pts
with diffuse large-B-cell lymphoma in advanced
follicular lymphoma

• Coiffier B et al. N Engl J Med 346 235-242, 2002
• R-CHOP is better than CHOP in elderly pts
  with diffuse large-B-cell lymphoma in terms of CR
  rate, DFS, and OS, without a clinically
  significant increase in toxicity.
• (Pfreundschu M et al. Lancet Oncol 5 379-91,
  2006
• Similar conclusion for young pts with good
• prognosis).
• Hiddemann W et al. Blood 106 3725-32, 2005
• Similar conclusion for advanced follicular
  lymphoma

71
Intensive chemotherapy (ACVBP) vs.3 cycles of
CHOP radiotherapy in localized stage I/II
aggressive NHL in pts lt 61 yrs without
prognostic factors

• Reyes F et al. N Engl J Med 352 1197-205, 2005
• Chemo alone was superior in terms of event free
  survival and overall survival.

72
Urological Tumors

• Neoadjuvant chemo plus cystectomy vs. cystectomy
  alone for locally advanced bladder cancer.
• Randomized trials of docetaxel in hormone
  refractory prostate cancer.

73
Neoadjuvant chemo plus cystectomy vs. cystectomy
alone for locally advanced bladder cancer

• Grossman HB et al. Neoadjuvant chemotherapy plus
  cystectomy compared with cystectomy alone for
  locally advanced bladder cancer. N Engl J Med
  349 859-66, 2003
• Neoadjuvant chemo (MVAC) increases the
  likelihood of eliminating residual cancer in the
  cystectomy specimen and increases survival.

74
Randomized trials of docetaxel in hormone
refractory prostate cancer

• Tannock IF et al. Docetaxel plus prednisone or
  mitoxantrone plus prednisone for advanced
  prostatic cancer. N Engl J Med 351 1502-12, 2004
• Petrylak DP et al. Docetaxel and estramustine
  compared with mitoxantrone and prednisone for
  advanced refractory prostate cancer. N Engl J Med
  351 1513-20, 2004
• improved survival (both articles) and improved
  rates of response in terms of pain, serum PSA
  level, and QOL (Tannock IF et al.) for the
  docetaxel-containing regimens.