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<strong>ION</strong> <strong>Solutions</strong>National Physician Network<strong>Pathways</strong>November 2012

Neoadjuvant <strong>Breast</strong>: HER2/neu NegativeHormone Therapy (for hormone receptor positive tumors only):Aromatase InhibitorAnastrozole 1mg PO q D x 5 yearsExemestane 25mg PO q D x 5 yearsLetrozole 2.5mg PO q D x 5 years>> JCO 26:1059-1065, 2008Chemotherapy:Adriamycin (Doxorubicin) Cytoxan (Cyclophosphamide) Followed by Taxotere(Docetaxel) EP=High; FN=10%-20%Doxorubicin 60mg/m2 IVP D1Cyclophosphamide 600mg/m2 D1q 14 or 21 Day Cycle x 4 CyclesFollowed by:Docetaxel 100 mg/m2 D1q 21 Day Cycle x 4 Cycles>> JCO 24: 5381-5387, 2006>> Surgical Clinics of North America 83:943-971, 2003DOSE DENSE Adriamycin (Doxorubicin) Cytoxan (Cyclophosphamide) Followed byDOSE DENSE Taxol (Paclitaxel) EP=High; FN˃20%Doxorubicin 60mg/m2 D1Cyclophosphamide 600mg/m2 D1q 14 Day Cycle x 4 CyclesFollowed by:Paclitaxel 175mg/ m2 D1 (or weekly equivalent)q 14 Day Cycle x 4 Cycles>> J Clin Onc 21: 1431-9, 2003Taxotere (Docetaxel) Cytoxan (Cyclophosphamide) EP=Moderate; FN˃20%Docetaxel 75mg/m 2 D1Cyclophosphamide 600mg/m 2 D1q 21 Day Cycle x 4 Cycles>> San Antonio <strong>Breast</strong> <strong>Cancer</strong> Symposium. Abstract 12, 2007Taxotere (Docetaxel) Adriamycin (Doxorubicin) Cytoxan (Cyclophosphamide)EP=High; FN˃20%Docetaxel 75mg/m 2 D1Doxorubicin 50mg/m 2 D1Cyclophosphamide 500mg/m 2 D1q 21 Day Cycle x 6 Cycles>> N Engl J Med 352: 22, 2005<strong>Clinical</strong> Trial:Screen patient for clinical trial. Check www.clinicaltrials.gov for available trials.Page 2 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Best Supportive Care and/or Hospice:Consider supportive care options and Hospice when appropriate.Neoadjuvant <strong>Breast</strong>: HER2/neu PositiveHormone Therapy (for hormone receptor positive tumors only):Aromatase InhibitorAnastrozole 1mg PO q D x 5 yearsExemestane 25mg PO q D x 5 yearsLetrozole 2.5mg PO q D x 5 years>> JCO 26:1059-1065, 2008Zoladex (Goserelin)Goserelin 3.6 mg SQ q MonthNote: Ovarian suppression>> Lancet 369: 1711, 2007Chemotherapy:Taxotere (Docetaxel) Paraplatin (Carboplatin) Herceptin (Trastuzumab) EP=Moderate;FN˃20%Docetaxel 75mg/m2 D1Carboplatin AUC 6 D1Trastuzumab 8mg/kg D1 Cycle 1 only6mg/kgD1 (or weekly equivalent)q 21 Day Cycle x 6 CyclesFollowed by:Trastuzumab 6mg/kg D1q 21 Day Cycle x 11 Cycles>> JCO 25:2678- 2684, 2007Adriamycin (Doxorubicin) Cytoxan (Cyclophosphamide) Followed by Taxol(Paclitaxel) Herceptin (Trastuzumab) EP=High; FN=10%-20%Doxorubicin 60mg/m2 D1Cyclophosphamide 600mg/m2 D1q 21 Day Cycle x 4 CyclesFollowed by:Paclitaxel 80mg/m2 D1Trastuzumab 4mg/kg D1 Cycle 1 only2mg/kgD1q 7 Day Cycle x 12 CyclesThen continue:Trastuzumab 6mg/kg D1q 21 Day Cycle x 13 Cycles>> NEJM 353: 1673-1684, 2005Page 3 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Cytoxan (Cyclophosphamide) Methotrexate 5-FU (5-Fluorouracil) EP=Moderate;FN=10%-20%Cyclophosphamide 100mg/m 2 PO D1-14 (or IV equivalent)Methotrexate 40mg/m 2 D1, D85-Fluorouracil 600mg/m 2 D1, D8q 28 Day Cycle x 6 Cycles>> Ann Oncol 9:489-93, 1998<strong>Clinical</strong> Trial:Screen patient for clinical trial. Check www.clinicaltrials.gov for available trials.Best Supportive Care and/or Hospice:Consider supportive care options and Hospice when appropriate.Note: For women with node negative, ER/PR positive tumors, Oncotype DXshould be considered as aid to determine who might benefit from cytotoxicadjuvant chemotherapy.Adjuvant <strong>Breast</strong>: Node Negative or Node Positive (High Risk)Hormone Therapy:Nolvadex (Tamoxifen)Tamoxifen 20mg PO q D x 5 years>> J Natl <strong>Cancer</strong> Inst 91:1829-1846, 1999Aromatase Inhibitor (plus ovarian ablation for premenopausal women)Anastrozole 1mg PO q D x 5 yearsExemestane 25mg PO q D x 5 yearsLetrozole 2.5mg PO q D x 5 years>> J Clin Oncol 26:1059-1065, 2008Nolvadex (Tamoxifen) Followed by Aromatase InhibitorTamoxifen 20mg PO q DFollowed by one of the following AI’s:Anastrozole 1mg PO q DExemestane 25mg PO q DLetrozole 2.5mg PO q D>> J Natl <strong>Cancer</strong> Inst 2005; 97:1262-1271Zoladex (Goserelin)Goserelin 3.6 mg SQ q MonthNote: Ovarian suppression>> Lancet 369: 1711, 2007Page 5 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Chemotherapy:Taxotere (Docetaxel) Adriamycin (Doxorubicin) Cytoxan (Cyclophosphamide)EP=High; FN˃20%Docetaxel 75mg/m 2 D1Doxorubicin 50mg/m 2 D1Cyclophosphamide 500mg/m 2 D1q 21 Day Cycle x 6 Cycles>> N Engl J Med 352: 22, 2005DOSE DENSE Adriamycin (Doxorubicin) Cytoxan (Cyclophosphamide) Followed byDOSE DENSE Taxol (Paclitaxel) EP=High; FN˃20%Doxorubicin 60mg/m 2 IVP D1Cyclophosphamide 600mg/m 2 D1q 14 Day Cycle x 4 CyclesFollowed by:Paclitaxel 175mg/ m 2 D1q 14 Day Cycle x 4 Cycles>> J Clin Oncol 21:1431-1439, 2003Taxotere (Docetaxel) Cytoxan (Cyclophosphamide) EP=Moderate; FN˃20%Docetaxel 75mg/m 2 D1Cyclophosphamide 600mg/m 2 D1q 21 Day Cycle x 4 Cycles>> San Antonio <strong>Breast</strong> <strong>Cancer</strong> Symposium. Abstract 12, 2007Adriamycin (Doxorubicin) Cytoxan (Cyclophosphamide) Followed by Taxotere(Docetaxel) EP=High; FN=10%-20%Doxorubicin 60mg/m 2 IVP D1Cyclophosphamide 600mg/m 2 D1q 21 Day Cycle x 4 CyclesFollowed by:Docetaxel 100 mg/m 2 D1q 21 Day Cycle x 4 Cycles>> N Engl J Med 258:1663-1671, 2008<strong>Clinical</strong> Trial:Screen patient for clinical trial. Check www.clinicaltrials.gov for available trials.Best Supportive Care and/or Hospice:Consider supportive care options and Hospice when appropriate.Page 6 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Adjuvant <strong>Breast</strong>: HER2/neu Positive (High or Low Risk)Hormone Therapy:Nolvadex (Tamoxifen)Tamoxifen 20mg PO q D x 5 years>> J Natl <strong>Cancer</strong> Inst 91:1829-1846, 1999Aromatase Inhibitor (plus ovarian ablation for premenopausal women)Anastrozole 1mg PO q D x 5 yearsExemestane 25mg PO q D x 5 yearsLetrozole 2.5mg PO q D x 5 years>> J Clin Oncol 26:1059-1065, 2008Nolvadex (Tamoxifen) Followed by Aromatase InhibitorTamoxifen 20mg PO q DFollowed by one of the following AI’s:Anastrozole 1mg PO q DExemestane 25mg PO q DLetrozole 2.5mg PO q D>> J Natl <strong>Cancer</strong> Inst 2005; 97:1262-1271Zoladex (Goserelin)Goserelin 3.6 mg SQ q MonthNote: Ovarian suppression>> Lancet 369: 1711, 2007Chemotherapy:Adriamycin (Doxorubicin) Cytoxan (Cyclophosphamide) Followed by Taxol(Paclitaxel) Herceptin (Trastuzumab) EP=High; FN=10%-20%Doxorubicin 60mg/m 2 D1Cyclophosphamide 600mg/m 2 D1q 21 Day Cycle x 4 CyclesFollowed by:Paclitaxel 80mg/m 2 D1, D8, D15Trastuzumab 4mg/kg D1 (Cycle 1 only)2mg/kgD1, D8, D15q 21 Day Cycle x 4 CyclesThen continue:Trastuzumab 6mg/kg D1q 21 Day Cycle x 13 Cycles>> N Engl J Med 353:1673-1684, 2005Page 7 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Taxotere (Docetaxel) Paraplatin (Carboplatin) Herceptin (Trastuzumab) EP=Moderate;FN˃20%Docetaxel 75mg/m 2 D1Carboplatin AUC 6 D1Trastuzumab 4mg/kg D1 (Cycle 1 only)2mg/kgD1, D8, D15q 21 Day Cycle x 6 CyclesThen continue:Trastuzumab 6mg/kg D1q 21 Day Cycle to complete 1 year of therapy>> J Clin Oncol 25:18S (June 20 suppl) Abstract 19647, 2007Adriamycin (Doxorubicin) Cytoxan (Cyclophosphamide) Followed by Taxotere(Docetaxel) Herceptin (Trastuzumab) EP=High; FN=10%-20%Doxorubicin 60mg/m2 D1Cyclophosphamide 600mg/m2 D1q 14 or q 21 Day Cycle x 4 CyclesFollowed by:Docetaxel 100 mg/m 2 D1Trastuzumab 4mg/kg D1 (Cycle 1 only)2mg/kgD1, D8, D15q 21 Day Cycle x 4 CyclesThen continue:Trastuzumab 6mg/kg D1q 21 Day Cycle x 13 Cycles>> NEnglJMed2005Oct;353(16):1673-84Taxotere (Docetaxel) Cytoxan (Cyclophosphamide) Herceptin (Trastuzumab)EP=Moderate; FN˃20%Docetaxel 75mg/m2 D1Cyclophosphamide 600mg/m2 D1Trastuzumab 8mg/kg D1 (Cycle 1 only)6mg/kgD1 (or weekly equivalent)q 21 Day Cycle x 4 or 6 CyclesThen continue:Trastuzumab 6mg/kg D1q 21 Day Cycle to complete 1 year of therapy>> JClinOncol2006Dec1;24(34):5381-7<strong>Clinical</strong> Trial:Screen patient for clinical trial. Check www.clinicaltrials.gov for available trials.Best Supportive Care and/or Hospice:Consider supportive care options and Hospice when appropriate.Page 8 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Metastatic <strong>Breast</strong>: HER2/neu NegativeHormone Therapy:Nolvadex (Tamoxifen)Tamoxifen 20mg PO q D>> J Natl <strong>Cancer</strong> Inst 91:1829-1846, 1999Aromatase Inhibitor (plus ovarian ablation for premenopausal women)Anastrozole 1mg PO q DExemestane 25mg PO q DLetrozole 2.5mg PO q D>> J Clin Oncol 26:1059-1065, 2008Faslodex (Fulvestrant)Fulvestrant 500mg IM D1, D15, D29 then Monthly>> J Clin Oncol 28:4594-4600, 2010Zoladex (Goserelin)Goserelin 3.6 mg SQ q MonthNote: Ovarian suppression>> Lancet 369: 1711, 2007Afinitor (Everolimus) Aromasin (Exemestane)Everolimus 10mg PO q DExemestane 25mg PO q DNote: only to be used second line after non-steriodal aromatase inhibitor>> NEJM 366:520-29, 2012Chemotherapy:Adriamycin (Doxorubicin) EP=High; FN> J Clin Oncol 17:2341-2454, 1999>> Eur J <strong>Cancer</strong> Clin Oncol 22:1431-1434, 1986Doxil (Pegylated Liposomal Encapsulated Doxorubicin) EP=Low; FN> Ann Ancol 15(3):440-449, 2004Taxol (Paclitaxel) EP=Low; FN=10%-20%Paclitaxel 80mg/m 2 D1, D8, D15 (or q3wk equivalent)q 21 Day Cycle>> J Clin Oncol 13:2575-2581, 1995>> J Clin Oncol 19:4216-4223, 2001Page 9 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Taxotere (Docetaxel) EP=Low; FN=10%-20%Docetaxel 40mg/m 2 D1, D8, D15, D22 (or q3wk equivalent)q 42 Day Cycle>> Semin Oncol 26:1-6, 1999>> Semin Oncol 24(Suppl 13):S11-18, 1997Abraxane (Paclitaxel Albumin-Bound) EP=Low; FN> J Clin Oncol 23:7794-7803, 2005>> J Clin Oncol 25(June 20 suppl):Abstract 1032, 2007Xeloda (Capecitabine)Capecitabine 1000-1250mg/m 2 PO BID D1-14q 21 Day Cycle>> J Clin Oncol 23:2155-2161, 2005 Epub 2005 Feb 14Gemzar (Gemcitabine) EP=Low; FN> Oncology (WillistonPark) 15(Suppl 3):11-4, 2001Navelbine (Vinorelbine) EP=Minimal; FN> <strong>Cancer</strong> 92:2267-2272, 2001Halaven (Eribulin Mesylate) EP=Low; FN> FDA LabelIxempra (Ixabepilone) EP=Low; FN> J Clin Oncol 25:3407-3414, 2007Taxotere (Docetaxel) Xeloda (Capecitabine) EP=Low; FN˃20%Docetaxel 75mg/m 2 D1Capecitabine 950mg/m 2 PO BID D1-14q 21 Day Cycle>> J Clin Oncol 20:2812-2823, 2002Gemzar (Gemcitabine) Taxol (Paclitaxel) EP=Low; FN=10%-20%Gemcitabine 1250mg/m 2 D1, D8Paclitaxel 175mg/m 2 D1q 21 Day Cycle>> J Clin Oncol 22 No 14S:510, 2004Page 10 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Ixempra (Ixabepilone) Xeloda (Capecitabine) EP=Low; FN=10%-20%Ixabepilone 40mg/m 2 D1Capecitabine 2000mg/m 2 PO BID D1-14q 21 Day Cycle>> J Clin Oncol 25:5210-5217, 2007Paraplatin (Carboplatin) EP=Moderate; FN> No reference needed as will only be used as a doublet.Cytoxan (Cyclophosphamide) EP=Moderate; FN˃20%Cyclophosphamide 600mg/m2 D1q 21 Day CycleNote: To be used in combination with docetaxel.>> JClinOncol2006Dec1;24(34):5381-7<strong>Clinical</strong> Trial:Screen patient for clinical trial. Check www.clinicaltrials.gov for available trials.Best Supportive Care and/or Hospice:Consider supportive care options and Hospice when appropriate.Note: For patients with visceral crisis, chemotherapy with a combination of activeagents is appropriate.Note: Treatment for PS≥4 will be considered off pathway.Metastatic <strong>Breast</strong>: HER2/neu PositiveHormone Therapy:Nolvadex (Tamoxifen)Tamoxifen 20mg PO q D>> J Natl <strong>Cancer</strong> Inst 91:1829-1846, 1999Aromatase Inhibitor (plus ovarian ablation for premenopausal women)Anastrozole 1mg PO q DExemestane 25mg PO q DLetrozole 2.5mg PO q D>> J Clin Oncol 26:1059-1065, 2008Page 11 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Herceptin (Trastuzumab) Followed by Nolvadex (Tamoxifen) or Aromatase InhibitorTrastuzumab 4mg/kg D1 (Cycle 1 only)2mg/kgD1, D8, D15q 21 Day CycleFollowed by one of the following:Tamoxifen 20mg PO q DAnastrozole 1mg PO q DExemestane 25mg PO q DLetrozole 2.5mg PO q D>> N Engl J Med 353:1659-1672, 2005Faslodex (Fulvestrant)Fulvestrant 500mg IM D1, D15, D29 then Monthly>> J Clin Oncol 28:4594-4600, 2010Zoladex (Goserelin)Goserelin 3.6 mg SQ q MonthNote: Ovarian suppression>> Lancet 369: 1711, 2007Chemotherapy:Herceptin (Trastuzumab) Paraplatin (Carboplatin) Taxol (Paclitaxel) EP=Moderate;FN˃20%Trastuzumab 4mg/kg D1 (Cycle 1 only)2mg/kgD1, D8, D15 (or q3wk equivalent)Carboplatin AUC 6 D1Paclitaxel 175mg/m 2 D1q 21 Day Cycle>> J Clin Oncol 24:2786-2792, 2004Herceptin (Trastuzumab) Taxol (Paclitaxel) EP=Low; FN=10%-20%Trastuzumab 4mg/kg D1 (Cycle 1 only)2mg/kgD1, D8, D15 (or q3wk equivalent)Paclitaxel 80-90mg/m 2 D1, D8, D15 (or q3wk equivalent)q 21 Day Cycle>> N Engl J Med 344:783-792, 2001>> J Clin Oncol 26:1642-1649, 2008Herceptin (Trastuzumab) Taxotere (Docetaxel) EP=Low; FN˃20%Trastuzumab 4mg/kg D1 (Cycle 1 only)2mg/kgD1, D8, D15 (or q3wk equivalent)Docetaxel 35mg/m 2 D1, D8, D15 (or q3wk equivalent)q 21 Day Cycle>> J Clin Oncol 23:4265-4274, 2005>> J Clin Oncol 20:1800-1808, 2002Page 12 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Herceptin (Trastuzumab) Navelbine (Vinorelbine) EP=Minimal; FN> <strong>Cancer</strong> 110:965-972, 2007Herceptin (Trastuzumab) Xeloda (Capecitabine) EP=Low; FN> J Clin Oncol 25:3853-3858, 2007Xeloda (Capecitabine) Tykerb (Lapatinib)Capecitabine 1000mg/m 2 PO BID D1-14Lapatinib 1250mg PO D1-21q 21 Day Cycle>> N Engl J Med 355:2733-2743, 2006Herceptin (Trastuzumab) Tykerb (Lapatinib) EP=Low; FN> J Clin Oncol 26 (May 20 suppl): Abstract 1015, 2008Herceptin (Trastuzumab) EP=Minimal; FN> AmJHealthSystPharm2008May15;65(10Suppl3):S4-9Herceptin (Trastuzumab) Gemzar (Gemcitabine) Paraplatin (Carboplatin)EP=Moderate; FN=10%-20%Trastuzumab 8mg/kg D0 (Cycle 1 only)6mg/kgD1Gemcitabine 1000mg/m2 D1, D8Carboplatin AUC 4-5 D1q 21 Day Cycle>> Clin<strong>Breast</strong><strong>Cancer</strong>2008;8(5):425-431Page 13 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Herceptin (Trastuzumab) Taxotere (Docetaxel) Paraplatin (Carboplatin) EP=Moderate;FN˃20%Trastuzumab 6mg/kg D1 (or weekly equivalent)Docetaxel 75mg/m2 D1 (D2 Cycle 1 only)Carboplatin AUC 6 D1 (D2 Cycle 1 only)q 21 Day Cycle x 6 CyclesThen continue:Trastuzumab 6mg/kg D1q 21 Day Cycle to complete 1 year of therapy>> JNatl<strong>Cancer</strong>Inst2004May19;96(10):739-49Tykerb (Lapatinib)Lapatinib 1250mg PO q DNote: 3 rd line or greater with cytotoxic chemotherapy>> Package InsertFemara (Letrozole) Tykerb (Lapatinib)Letrozole 2.5mg PO q DLapatinib 1500mg PO q D>> J Clin Onc 27: 5538-46, 2009Perjeta (Pertuzumab) Herceptin (Trastuzumab) Taxotere (Docetaxel) EP=Low;FN˃20%Pertuzumab 840mg D1 (Cycle 1 only)420mgD1Trastuzumab 8mg/kg D1 (Cycle 1 only)6mg/kgD1Docetaxel 75mg/m2 D1q 21 Day CycleNote: First line only>> FDA Label<strong>Clinical</strong> Trial:Screen patient for clinical trial. Check www.clinicaltrials.gov for available trials.Best Supportive Care and/or Hospice:Consider supportive care options and Hospice when appropriate.Note: Herceptin (Trastuzumab) can be used with any accepted breast cancerchemotherapy except anthracycline and appropriate to continue until diseaseprogression.Page 14 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Adjuvant ColonChemotherapy:mFOLFOX 6 EP=Moderate; FN=10%-20%Oxaliplatin 85mg/m 2 D1, D15Leucovorin 400mg/m 2 D1, D155-Fluorouracil 400mg/m 2 IVP D1, D155-Fluorouracil2400mg/m 2 CI over 46 hours D1, D15q 28 Day Cycle x 6 Cycles>> J Clin Oncol 26:2006-2012, 2008Xeloda (Capecitabine)Capecitabine 1250mg/m 2 PO BID D1-14q 21 Day Cycle x 8 Cycles>> N Engl J Med 352:2696-2704, 2005CapeOx EP=Moderate; FN> J Clin Oncol 25:102-109, 2007>> J Clin Oncol 29:1465-1471, 20115-FU (5-Fluorouracil) Leucovorin EP=Low; FN> J Clin Oncol 23:8671-8678, 2005>> Eur J <strong>Cancer</strong> 35:1343-1347, 1999FLOX EP=Moderate; FN=10%-20%5-Fluorouracil 500mg/m2 D1, D8, D15, D22, D29, D36Leucovorin 500mg/m2 D1, D8, D15, D22, D29, D36Oxaliplatin 85mg/m2 D1, D15, D29q 56 Day Cycle x 3 Cycles>> J Clin Onc 25:2198-2204,2007<strong>Clinical</strong> Trial:Screen patient for clinical trial. Check www.clinicaltrials.gov for available trials.Best Supportive Care and/or Hospice:Consider supportive care options and Hospice when appropriate.Page 15 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Colon: First Line MetastaticChemotherapy:mFOLFOX 6 +/- Avastin (Bevacizumab) EP=Moderate; FN=10%-20%Oxaliplatin 85mg/m 2 D1, D15Leucovorin 400mg/m 2 D1, D155-Fluorouracil 400mg/m 2 IVP D1, D155-Fluorouracil 2400mg/m 2 CI over 46 hours D1, D15+/- Bevacizumab 5mg/kg D1, D15q 28 Day Cycle>> J Clin Oncol 26:2006-2012, 2008>> Br J <strong>Cancer</strong> 87:393-399, 2002>> BMC <strong>Cancer</strong> 7:91, 2007CapeOx +/- Avastin (Bevacizumab) EP=Moderate; FN> J Clin Oncol 26:2006-2012, 2008>> J Clin Oncol 26:2013-2019, 2008FOLFIRI +/- Avastin (Bevacizumab) EP=Moderate; FN=10%-20%Irinotecan 180mg/m 2 D1, D15Leucovorin 400mg/m 2 D1, D155-Fluorouracil 400mg/m 2 IVP D1, D155-Fluorouracil 2400mg/m 2 CI over 46 hours D1, D15+/- Bevacizumab 5mg/kg D1, D15q 28 Day Cycle>> Eur J <strong>Cancer</strong> 35:1343-1347, 1999>> J Clin Oncol 25:4779-4786, 20075-FU (5-Fluorouracil) Leucovorin +/- Avastin (Bevacizumab) EP=Low; FN> J Clin Oncol 11:1879-1887, 1993>> Eur J <strong>Cancer</strong> 35:1343-1347, 1999>> The Lancet 355:1041-1047, 2000CapIri +/- Avastin (Bevacizumab) EP=Moderate; FN˃20%Irinotecan 80mg/m2 D1, D8(May be given as 250mg/m2 on D1 only)Capecitabine 1000mg/m2 PO BID D1-14+/- Bevacizumab 7.5mg/kg D1q 21 Day Cycle>> WorldJGastroenterol2009January28;15(4):449–456Page 16 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Xeloda (Capecitabine) +/- Avastin (Bevacizumab) EP=Low; FN> J Clin Onc19:4097-4106,2001<strong>Clinical</strong> Trial:Screen patient for clinical trial. Check www.clinicaltrials.gov for available trials.Best Supportive Care and/or Hospice:Consider supportive care options and Hospice when appropriate.Colon: Second Line MetastaticChemotherapy:mFOLFOX 6 +/- Avastin (Bevacizumab) EP=Moderate; FN=10%-20%Oxaliplatin 85mg/m 2 D1, D15Leucovorin 400mg/m 2 D1, D155-Fluorouracil 400mg/m 2 IVP D1, D155-Fluorouracil 2400mg/m 2 CI over 46 hours D1, D15+/- Bevacizumab 5mg/kg D1, D15q 28 Day Cycle>> J Clin Oncol 26:2006-2012, 2008>> Br J <strong>Cancer</strong> 87:393-399, 2002>> BMC <strong>Cancer</strong> 7:91, 2007CapeOx +/- Avastin (Bevacizumab) EP=Moderate; FN> J Clin Oncol 26:2006-2012, 2008>> J Clin Oncol 26:2013-2019, 2008FOLFIRI +/- Avastin (Bevacizumab) EP=Moderate; FN=10%-20%Irinotecan 180mg/m 2 D1, D15Leucovorin 400mg/m 2 D1, D155-Fluorouracil 400mg/m 2 IVP D1, D155-Fluorouracil+/- Bevacizumab 5mg/kg D1, D15q 28 Day Cycle>> Eur J <strong>Cancer</strong> 35:1343-1347, 1999>> J Clin Oncol 25:4779-4786, 20072400mg/m 2 CI over 46 hours D1, D15Page 17 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

5-FU (5-Fluorouracil) Leucovorin +/- Avastin (Bevacizumab) EP=Low; FN> J Clin Oncol 11:1879-1887, 1993>> Eur J <strong>Cancer</strong> 35:1343-1347, 1999>> The Lancet 355:1041-1047, 2000CapIri +/- Avastin (Bevacizumab) EP=Moderate; FN˃20%Irinotecan 80mg/m2 D1, D8(May be given as 250mg/m2 on D1 only)Capecitabine 1000mg/m2 PO BID D1-14+/- Bevacizumab 7.5mg/kg D1q 21 Day Cycle>> WorldJGastroenterol2009January28;15(4):449–456Xeloda (Capecitabine) +/- Avastin (Bevacizumab) EP=Low; FN> J Clin Onc19:4097-4106,2001FOLFIRI +/- Erbitux (Cetuximab) EP=Moderate; FN=10%-20%Irinotecan 180mg/m 2 D1, D15Leucovorin 400mg/m 2 D1, D155-Fluorouracil 400mg/m 2 IVP D1, D155-Fluorouracil 2400mg/m 2 CI over 46 hours D1, D15+/- Cetuximab 400mg/m 2 D1 (Cycle 1 only)250mg/m 2 D1, D8, D15, D22 (or q2wk equivalent)q 28 Day Cycle>> Eur J <strong>Cancer</strong> 35:1343-1347, 1999>> Br J <strong>Cancer</strong> 99:455-458, 2008Camptosar (Irinotecan) EP=Moderate; FN> The Lancet 352:1413-1418, 1998>> J Clin Oncol 21:807-814, 2003Erbitux (Cetuximab) Camptosar (Irinotecan) EP=Moderate; FN> Br J <strong>Cancer</strong> 99:455-458, 2008>> Gastrointestinal <strong>Cancer</strong>s Symposium Abstract 237, 2007Page 18 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Camptosar (Irinotecan) Avastin (Bevacizumab) EP=Moderate; FN> TherAdvMedOncol2010Sep;2(5):309-17Camptosar (Irinotecan) Vectibix (Panitumumab) EP=Moderate; FN> NEnglJMed2004;351:337-345FOLFIRI Vectibix (Panitumumab) EP=Moderate; FN=10%-20%Irinotecan 180mg/m2 D1, D15Leucovorin 400mg/m2 D1, D155-Fluorouracil 400mg/m2 IVP D1, D155-Fluorouracil 2400mg/m2 CI over 46 hours D1, D15Panitumumab 6mg/kg D1, D15q 28 Day Cycle>> BrJ<strong>Cancer</strong>2008Aug5;99(3):455-8Erbitux (Cetuximab) EP=Minimal; FN> NEnglJMed2004;351:337-345Xeloda (Capecitabine) +/- Erbitux (Cetuximab) EP=Low; FN> JClinOncol2005Feb1;23(4):792-9>> J Clin Oncol 19:4097-4106, 2001>> J Clin Oncol 26:2013-2019, 2008FOLFIRI Zaltrap (Ziv-aflibercept) EP=Moderate; FN=10%-20%Irinotecan 180mg/m 2 D1, D15Leucovorin 400mg/m 2 D1, D155-Fluorouracil 400mg/m 2 IVP D1, D155-Fluorouracil 2400mg/m 2 CI over 46 hours D1, D15Ziv-aflibercept 4mg/kg D1, D15q 28 Day Cycle>> J Clin Oncol 30 (suppl):3505, 2012<strong>Clinical</strong> Trial:Screen patient for clinical trial. Check www.clinicaltrials.gov for available trials.Best Supportive Care and/or Hospice:Consider supportive care options and Hospice when appropriate.Page 19 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Note: Wild Type KRAS documentation is required for all newly metastatic casesbefore cetuximab or panitumumab is used.Note: 1 st line EGFR directed treatment must be cetuximab. Panitumumab maybe used 2 nd line or later with reaction or intolerance to cetuximab. A second lineof VEGF directed treatment (bevacizumab) is considered compliant if there is nodocumented failure.Colon: Third Line MetastaticChemotherapy:mFOLFOX 6 +/- Avastin (Bevacizumab) EP=Moderate; FN=10%-20%Oxaliplatin 85mg/m 2 D1, D15Leucovorin 400mg/m 2 D1, D155-Fluorouracil 400mg/m 2 IVP D1, D155-Fluorouracil 2400mg/m 2 CI over 46 hours D1, D15+/- Bevacizumab 5mg/kg D1, D15q 28 Day Cycle>> J Clin Oncol 26:2006-2012, 2008>> Br J <strong>Cancer</strong> 87:393-399, 2002>> BMC <strong>Cancer</strong> 7:91, 2007CapeOx +/- Avastin (Bevacizumab) EP=Moderate; FN> J Clin Oncol 26:2006-2012, 2008>> J Clin Oncol 26:2013-2019, 2008FOLFIRI +/- Avastin (Bevacizumab) EP=Moderate; FN=10%-20%Irinotecan 180mg/m 2 D1, D15Leucovorin 400mg/m 2 D1, D155-Fluorouracil 400mg/m 2 IVP D1, D155-Fluorouracil+/- Bevacizumab 5mg/kg D1, D15q 28 Day Cycle>> Eur J <strong>Cancer</strong> 35:1343-1347, 1999>> J Clin Oncol 25:4779-4786, 20072400mg/m 2 CI over 46 hours D1, D15Page 20 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

5-FU (5-Fluorouracil) Leucovorin +/- Avastin (Bevacizumab) EP=Low; FN> J Clin Oncol 11:1879-1887, 1993>> Eur J <strong>Cancer</strong> 35:1343-1347, 1999>> The Lancet 355:1041-1047, 2000CapIri +/- Avastin (Bevacizumab) EP=Moderate; FN˃20%Irinotecan 80mg/m2 D1, D8(May be given as 250mg/m2 on D1 only)Capecitabine 1000mg/m2 PO BID D1-14+/- Bevacizumab 7.5mg/kg D1q 21 Day Cycle>> WorldJGastroenterol2009January28;15(4):449–456Xeloda (Capecitabine) +/- Avastin (Bevacizumab) EP=Low; FN> J Clin Onc19:4097-4106,2001FOLFIRI +/- Erbitux (Cetuximab) EP=Moderate; FN=10%-20%Irinotecan 180mg/m 2 D1, D15Leucovorin 400mg/m 2 D1, D155-Fluorouracil 400mg/m 2 IVP D1, D155-Fluorouracil 2400mg/m 2 CI over 46 hours D1, D15+/- Cetuximab 400mg/m 2 D1 (Cycle 1 only)250mg/m 2 D1, D8, D15, D22 (or q2wk equivalent)q 28 Day Cycle>> Eur J <strong>Cancer</strong> 35:1343-1347, 1999>> Br J <strong>Cancer</strong> 99:455-458, 2008Camptosar (Irinotecan) EP=Moderate; FN> The Lancet 352:1413-1418, 1998>> J Clin Oncol 21:807-814, 2003Erbitux (Cetuximab) Camptosar (Irinotecan) EP=Moderate; FN> Br J <strong>Cancer</strong> 99:455-458, 2008>> Gastrointestinal <strong>Cancer</strong>s Symposium Abstract 237, 2007Page 21 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Camptosar (Irinotecan) Avastin (Bevacizumab) EP=Moderate; FN> TherAdvMedOncol2010Sep;2(5):309-17Camptosar (Irinotecan) Vectibix (Panitumumab) EP=Moderate; FN> NEnglJMed2004;351:337-345FOLFIRI Vectibix (Panitumumab) EP=Moderate; FN=10%-20%Irinotecan 180mg/m2 D1, D15Leucovorin 400mg/m2 D1, D155-Fluorouracil 400mg/m2 IVP D1, D155-Fluorouracil 2400mg/m2 CI over 46 hours D1, D15Panitumumab 6mg/kg D1, D15q 28 Day Cycle>> BrJ<strong>Cancer</strong>2008Aug5;99(3):455-8Erbitux (Cetuximab) EP=Minimal; FN> NEnglJMed2004;351:337-345Xeloda (Capecitabine) +/- Erbitux (Cetuximab) EP=Low; FN> JClinOncol2005Feb1;23(4):792-9>> J Clin Oncol 19:4097-4106, 2001>> J Clin Oncol 26:2013-2019, 2008Vectibix (Panitumumab) EP=Minimal; FN> J Clin Oncol 25:1658-1664, 2007Stivarga (Regorafenib)Regorafenib 160mg PO D1-21q 28 Day Cycle>> J Clin Oncol 30 (suppl 4):LBA385, 2012<strong>Clinical</strong> Trial:Screen patient for clinical trial. Check www.clinicaltrials.gov for available trials.Best Supportive Care and/or Hospice:Consider supportive care options and Hospice when appropriate.Page 22 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Note: Wild Type KRAS documentation is required for all newly metastatic casesbefore cetuximab or panitumumab is used.Note: 1 st line EGFR directed treatment must be cetuximab. Panitumumab maybe used 2 nd line or later with reaction or intolerance to cetuximab. A second lineof VEGF directed treatment (bevacizumab) is considered compliant if there is nodocumented failure.Page 23 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Adjuvant Non-Small Cell Lung (NSCL)Chemotherapy:Platinol (Cisplatin) Navelbine (Vinorelbine) EP=High; FN=10%-20%Cisplatin 100mg/m 2 D1 (or D1, D8 protocol equivalent)Vinorelbine 30mg/m 2 D1, D8, D15, D22q 28 Day Cycle x 4 Cycles>> N Engl J Med 352:2589-2597, 2005>> N Engl J Med 350:351-360, 2004>> Lancet Oncol 7:71+-727, 2006Platinol (Cisplatin) Gemzar (Gemcitabine) EP=High; FN> Ann Oncol 18:317-323, 2007>> N Engl J Med 346:92-98, 2002Platinol (Cisplatin) Taxotere (Docetaxel) EP=High; FN=10%-20%Cisplatin 75mg/m 2 D1Docetaxel 75mg/m 2 D1q 21 Day Cycle x 4 Cycles>> J Clin Oncol 21:3016-3024, 2003 Epub 2003 Jul 1Platinol (Cisplatin) Alimta (Pemetrexed) EP=High; FN> J Clin Oncol 29: 2011 (suppl; abstr 7002)Taxol (Paclitaxel) Paraplatin (Carboplatin) EP=Moderate; FN=10%-20%Paclitaxel 200mg/m 2 D1Carboplatin AUC 6 D1q 21 Day Cycle x 4 Cycles>> J Clin Oncol 26:5043-5051, 2008Platinol (Cisplatin) Taxol (Paclitaxel) EP=High; FN˃20%Cisplatin 75mg/m2 D1Paclitaxel 200mg/m2 D1q 21 Day Cycle x 4 Cycles>> NEnglJMed2002Jan10;346(2):92-8>> JClinOncol2008Nov1;26(31):5043-51<strong>Clinical</strong> Trial:Screen patient for clinical trial. Check www.clinicaltrials.gov for available trials.Best Supportive Care and/or Hospice:Consider supportive care options and Hospice when appropriate.Page 24 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Note: Carboplatin may be used if comorbidities exist that prevent the use ofCisplatin.Non-Small Cell Lung (NSCL): Stage 3 Neoadjuvant or DefinitiveChemotherapy RadiationChemotherapy:Platinol (Cisplatin) VP-16 (Etoposide) XRT EP=HighCisplatin 50mg/m 2 D1, D8, D29, D36Etoposide 50mg/m 2 D1-5, D29-33XRTq 42 Day cycle>> J Clin Oncol 20:3454-3460, 2002Taxol (Paclitaxel) Paraplatin (Carboplatin) XRT EP=ModeratePaclitaxel 45-50mg/m 2 D1, D8, D15Carboplatin AUC 2 D1, D8, D15XRTq 21 Day CycleNote: May be followed by further chemotherapy.>> J Clin Oncol 23:5883-5891, 2005<strong>Clinical</strong> Trial:Screen patient for clinical trial. Check www.clinicaltrials.gov for available trials.Best Supportive Care and/or Hospice:Consider supportive care options and Hospice when appropriate.Non-Small Cell Lung (NSCL): First Line MetastaticChemotherapy:Paraplatin (Carboplatin) Taxol (Paclitaxel) +/- Avastin (Bevacizumab) EP=Moderate;FN=10%-20%Carboplatin AUC 6 D1Paclitaxel 200mg/m 2 D1+/- Bevacizumab 15mg/kg D1q 21 Day Cycle>> N Engl J Med 355:2542-2550, 2006Page 25 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Paraplatin (Carboplatin) Taxotere (Docetaxel) +/- Avastin (Bevacizumab)EP=Moderate; FN=10%-20%Carboplatin AUC 6 D1Docetaxel 75mg/m 2 D1+/- Bevacizumab 15mg/kg D1q 21 Day Cycle>> J Clin Oncol 21:3016-3024, 2003>> Oncologist 15:1102-1112, 2010Paraplatin (Carboplatin) Gemzar (Gemcitabine) +/- Avastin (Bevacizumab)EP=Moderate; FN> J Clin Oncol 27:3217-3224, 2009Paraplatin (Carboplatin) Alimta (Pemetrexed) +/- Avastin (Bevacizumab)EP=Moderate; FN> J Clin Oncol 27:3217-3224, 2009>> J Thorac Oncol 6:506-512, 2006Navelbine (Vinorelbine) EP=Minimal; FN> J Clin Oncol 12:360-367, 1994>> J Clin Oncol 18:2354-2362, 2000Tarceva (Erlotinib)Erlotinib 150mg PO q DNote: Erlotinib is considered for first line when EGFR mutation is documented or inappropriate clinical picture (Asian, female, never-smoker, bronchioalveolar.)>> N Engl J Med 353:123-132, 2005Xalkori (Crizotinib)Crizotinib 250mg PO BID q DNote: indicated as a first line therapy for ALK+>> J Clin Oncol 29 (suppl abstract 7507), 2011Gemzar (Gemcitabine) Navelbine (Vinorelbine) EP=Low; FN> J Clin Oncol 22:2348-2356, 2004Page 26 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Gemzar (Gemcitabine) Taxotere (Docetaxel) EP=Low; FN=10%-20%Gemcitabine 1100mg/m 2 D1, D8Docetaxel 100mg/m 2 D8q 21 Day Cycle>> Lancet 357:1478-1484, 2001<strong>Clinical</strong> Trial:Screen patient for clinical trial. Check www.clinicaltrials.gov for available trials.Best Supportive Care and/or Hospice:Consider supportive care options and Hospice when appropriate.Note: Continuation of Bevacizumab, Pemetrexed or Gemcitabine beyond 4-6cycles and in the absence of disease progression is considered continuationmaintenance therapy.Note: Platinol (Cisplatin) is an appropriate substitution for Paraplatin(Carboplatin) in select patients.Note: For patient to receive Bevacizumab they must NOT have any of thefollowing: squamous cell carcinoma; clinically significant hemoptysis; receivinganticoagulants.Note: Drugs approved for second line metastatic disease for patients withcomorbidities precluding combination treatment.Note: Bevacizumab used with any appropriate combination is consideredcompliant.Non-Small Cell Lung (NSCL): Switch Maintenance TherapyMaintenance Therapy:Alimta (Pemetrexed) EP=Low; FN> Lancet 374:1432-40, 2009Tarceva (Erlotinib)Erlotinib 150mg PO q D>> Lancet Oncol 11:521, 2010<strong>Clinical</strong> Trial:Screen patient for clinical trial. Check www.clinicaltrials.gov for available trials.Page 27 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Best Supportive Care and/or Hospice:Consider supportive care options and Hospice when appropriate.Note: Switch maintenance refers to the initiation of a different agent, not includedas a part of the first-line regimen, in the absence of disease progression, after 4-6 cycles of initial therapy.Non-Small Cell Lung (NSCL): Second Line MetastaticChemotherapy:Taxotere (Docetaxel) EP=Low; FN=10%-20%Docetaxel 75mg/m 2 D1q 21 Day Cycle>> J Clin Oncol 18:2354-2362, 2000Navelbine (Vinorelbine) EP=Minimal; FN> J Clin Oncol 18:2354-2362, 2000Gemzar (Gemcitabine) EP=Low; FN> J Clin Oncol 23:8380-8388, 2005Alimta (Pemetrexed) EP=Low; FN> J Clin Oncol 22:1589-1597, 2004>> J Clin Oncol 26:3543-3551, 2008Tarceva (Erlotinib)Erlotinib 150mg PO q D>> N Engl J Med 353:123-132, 2005Taxol (Paclitaxel) EP=Low; FN=10%-20%Paclitaxel 80mg/m2 D1, D15, D21q 28 Day Cycle>> <strong>Cancer</strong>1997;79:724-729Paraplatin (Carboplatin) Taxol (Paclitaxel) +/- Avastin (Bevacizumab) EP=Moderate;FN=10%-20%Carboplatin AUC 6 D1Paclitaxel 200mg/m2 D1+/- Bevacizumab 15mg/kg D1q 21 Day Cycle x 4-6 CyclesThen continue maintenance bevacizumab until disease progression>> NEJM 355:2542-2550,2006Page 28 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Paraplatin (Carboplatin) Alimta (Pemetrexed) EP=Moderate; FN> J Clin Onc 27: 3284, 2009<strong>Clinical</strong> Trial:Screen patient for clinical trial. Check www.clinicaltrials.gov for available trials.Best Supportive Care and/or Hospice:Consider supportive care options and Hospice when appropriate.Note: Treatment for PS≥3 will be considered off pathway.Non-Small Cell Lung (NSCL): Third Line MetastaticChemotherapy:Taxotere (Docetaxel) EP=Low; FN=10%-20%Docetaxel 75mg/m 2 D1q 21 Day Cycle>> J Clin Oncol 18:2354-2362, 2000Navelbine (Vinorelbine) EP=Minimal; FN> J Clin Oncol 18:2354-2362, 2000Gemzar (Gemcitabine) EP=Low; FN> J Clin Oncol 23:8380-8388, 2005Alimta (Pemetrexed) EP=Low; FN> J Clin Oncol 22:1589-1597, 2004>> J Clin Oncol 26:3543-3551, 2008Tarceva (Erlotinib)Erlotinib 150mg PO q D>> N Engl J Med 353:123-132, 2005Taxol (Paclitaxel) EP=Low; FN=10%-20%Paclitaxel 80mg/m2 D1, D15, D21q 28 Day Cycle>> <strong>Cancer</strong>1997;79:724-729Page 29 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

<strong>Clinical</strong> Trial:Screen patient for clinical trial. Check www.clinicaltrials.gov for available trials.Best Supportive Care and/or Hospice:Consider supportive care options and Hospice when appropriate.Note: Treatment for PS≥3 will be considered off pathway.Small Cell Lung: Limited DiseaseChemotherapy:Platinol (Cisplatin) VP-16 (Etoposide) XRT EP=HighCisplatin 60mg/m 2 D1Etoposide 120mg/m 2 D1-3ORCisplatin 80mg/m 2 D1Etoposide 100mg/m 2 D1-3XRTQ 21 Day Cycle>> N Engl J Med 340:265-271, 1999>> J Clin Oncol 24:5247-5252, 2006Paraplatin (Carboplatin) VP-16 (Etoposide) XRT EP=ModerateCarboplatin AUC 5-6 D1Etoposide 100mg/m 2 D1-3XRTq 21 Day Cycle>> Ann Oncol 12:1231-1238, 2001<strong>Clinical</strong> Trial:Screen patient for clinical trial. Check www.clinicaltrials.gov for available trials.Best Supportive Care and/or Hospice:Consider supportive care options and Hospice when appropriate.Page 30 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Small Cell Lung: Extensive Disease – First LineChemotherapy:Platinol (Cisplatin) VP-16 (Etoposide) EP=High; FN=10%-20%Cisplatin 75-80mg/m 2 D1Etoposide 80-100mg/m 2 D1-3ORCisplatin 25mg/m 2 D1-3Etoposide 100mg/m 2 D1-3q 21 Day Cycle>> J Clin Oncol 20 :4665-4672, 2002>> J Clin Oncol 12 :2022-2034, 1994>> J Clin Oncol 3:1471-1477, 1985Paraplatin (Carboplatin) VP-16 (Etoposide) EP=Moderate; FN=10%-20%Carboplatin AUC 5-6 D1Etoposide 100mg/m 2 D1-3q 21 Day Cycle>> J Clin Oncol 17:3540-3545, 1999Platinol (Cisplatin) Camptosar (Irinotecan) EP=High; FN=10%-20%Cisplatin 60mg/m 2 D1Irinotecan 60mg/m 2 D1, D8, D15q 28 Day CycleORCisplatin 30mg/m 2 D1, D8Irinotecan 65mg/m 2 D1, D8q 21 Day Cycle>> N Engl J Med 346:85-91, 2002>> J Clin Oncol 24:2038-2043, 2006<strong>Clinical</strong> Trial:Screen patient for clinical trial. Check www.clinicaltrials.gov for available trials.Best Supportive Care and/or Hospice:Consider supportive care options and Hospice when appropriate.Page 31 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Small Cell Lung: Extensive Disease – Second LineChemotherapy:Platinol (Cisplatin) VP-16 (Etoposide) EP=High; FN=10%-20%Cisplatin 75-80mg/m 2 D1Etoposide 80-100mg/m 2 D1-3ORCisplatin 25mg/m 2 D1-3Etoposide 100mg/m 2 D1-3q 21 Day Cycle>> J Clin Oncol 20 :4665-4672, 2002>> J Clin Oncol 12 :2022-2034, 1994>> J Clin Oncol 3:1471-1477, 1985Paraplatin (Carboplatin) VP-16 (Etoposide) EP=Moderate; FN=10%-20%Carboplatin AUC 5-6 D1Etoposide 100mg/m 2 D1-3q 21 Day Cycle>> J Clin Oncol 17:3540-3545, 1999Platinol (Cisplatin) Camptosar (Irinotecan) EP=High; FN=10%-20%Cisplatin 60mg/m 2 D1Irinotecan 60mg/m 2 D1, D8, D15q 28 Day CycleORCisplatin 30mg/m 2 D1, D8Irinotecan 65mg/m 2 D1, D8q 21 Day Cycle>> N Engl J Med 346:85-91, 2002>> J Clin Oncol 24:2038-2043, 2006Taxol (Paclitaxel) EP=Low, FN=10%-20%Paclitaxel 175mg/m 2 D1 (or weekly equivalent)q 21 Day Cycle>> Br J <strong>Cancer</strong> 77:347-351, 1998>> Anticancer Res 26:777-781, 2006Taxotere (Docetaxel) EP=Low; FN=10%-20%Docetaxel 100mg/m 2 D1 (or weekly equivalent)q 21 Day Cycle>> Eur J <strong>Cancer</strong> 30A:1058-1060, 1994Camptosar (Irinotecan) EP=Moderate; FN> J Clin Oncol 10:1225-1229, 1992Page 32 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Hycamtin (Topotecan) EP=Low; FN˃20%Topotecan 2.3mg/m 2 PO D1-5ORTopotecan 1.5mg/m 2 D1-5q 21 Day CycleORTopotecan 4mg/m 2 D1, D8, D15q 28 Day Cycle>> J Clin Oncol 17:658-667, 1999>> J Clin Oncol 24:5441-5447, 2006>> J Clin Oncol 25:2086-2092, 2007Gemzar (Gemcitabine) EP=Low; FN> J Clin Oncol 21:1550-1555, 2003>> Ann Oncol 12:557-561, 2001Hycamtin (Topotecan) Taxol (Paclitaxel) EP=Low; FN=10%-20%Topotecan 1.5mg/m2 D1-3Paclitaxel 135mg/m2 D1q 21 Day Cycle>> Oncologist: 8: 76-82, 2003<strong>Clinical</strong> Trial:Screen patient for clinical trial. Check www.clinicaltrials.gov for available trials.Best Supportive Care and/or Hospice:Consider supportive care options and Hospice when appropriate.Small Cell Lung: Extensive Disease – Third LineChemotherapy:Platinol (Cisplatin) VP-16 (Etoposide) EP=High; FN=10%-20%Cisplatin 75-80mg/m 2 D1Etoposide 80-100mg/m 2 D1-3ORCisplatin 25mg/m 2 D1-3Etoposide 100mg/m 2 D1-3q 21 Day Cycle>> J Clin Oncol 20 :4665-4672, 2002>> J Clin Oncol 12 :2022-2034, 1994>> J Clin Oncol 3:1471-1477, 1985Page 33 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Paraplatin (Carboplatin) VP-16 (Etoposide) EP=Moderate; FN=10%-20%Carboplatin AUC 5-6 D1Etoposide 100mg/m 2 D1-3q 21 Day Cycle>> J Clin Oncol 17:3540-3545, 1999Platinol (Cisplatin) Camptosar (Irinotecan) EP=High; FN=10%-20%Cisplatin 60mg/m 2 D1Irinotecan 60mg/m 2 D1, D8, D15q 28 Day CycleORCisplatin 30mg/m 2 D1, D8Irinotecan 65mg/m 2 D1, D8q 21 Day Cycle>> N Engl J Med 346:85-91, 2002>> J Clin Oncol 24:2038-2043, 2006Taxol (Paclitaxel) EP=Low, FN=10%-20%Paclitaxel 175mg/m 2 D1 (or weekly equivalent)q 21 Day Cycle>> Br J <strong>Cancer</strong> 77:347-351, 1998>> Anticancer Res 26:777-781, 2006Taxotere (Docetaxel) EP=Low; FN=10%-20%Docetaxel 100mg/m 2 D1 (or weekly equivalent)q 21 Day Cycle>> Eur J <strong>Cancer</strong> 30A:1058-1060, 1994Camptosar (Irinotecan) EP=Moderate; FN> J Clin Oncol 10:1225-1229, 1992Hycamtin (Topotecan) EP=Low; FN˃20%Topotecan 2.3mg/m 2 PO D1-5ORTopotecan 1.5mg/m 2 D1-5q 21 Day CycleORTopotecan 4mg/m 2 D1, D8, D15q 28 Day Cycle>> J Clin Oncol 17:658-667, 1999>> J Clin Oncol 24:5441-5447, 2006>> J Clin Oncol 25:2086-2092, 2007Gemzar (Gemcitabine) EP=Low; FN> J Clin Oncol 21:1550-1555, 2003>> Ann Oncol 12:557-561, 2001Page 34 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

VP-16 (Etoposide) EP=Low; FN=10%-20%Etoposide 50mg/m2 PO D1-21q 28 Day Cycle>> J Clin Onc 8:1613-1617,1990<strong>Clinical</strong> Trial:Screen patient for clinical trial. Check www.clinicaltrials.gov for available trials.Best Supportive Care and/or Hospice:Consider supportive care options and Hospice when appropriate.Page 35 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Anti-EmeticsEmetogenic Risk:High Emetic Risk5HT3 or palonosetron hydrochloride; steroid: and aprepitant or fosaprepitantModerate Emetic Risk5HT3 or palonosetron hydrochloride: steroid; +/- aprepitant or fosaprepitantLow Emetic RiskGeneric ondansetron or granisetronMinimal Emetic RiskAgent as listed belowMetaclopramide, lorazepam, prochlorazepine, h2 Blocker or proton pump inhibitor, steroidsand other non-5HT3 or non-aprepitant agents are optional and personalized.Compliance is only for the first cycle of any new line of treatment for chemotherapy forbreast, colon or lung.WBC SupportFebrile Neutropenia Risk:Febrile Neutropenia Risk ˃20%Administer CSFFebrile Neutropenia Risk 65, previous chemotherapy or radiationtherapy, poor performance status, renal or liver impairment, open wounds, preexistingneutropenia, bone marrow metastasis) with documentation.Compliance is only for the first cycle of any new line of treatment for chemotherapy forbreast, colon or lung.Page 36 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

<strong>Breast</strong> <strong>Cancer</strong>Colon <strong>Cancer</strong>Page 37 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Lung <strong>Cancer</strong>Page 38 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

Disclaimer<strong>Clinical</strong> pathways document potential steps in the diagnosis and treatment of acondition or procedure for individual patients. These are predominantlymanagement tools and are based on clinical information developed in otherguidelines or parameters and agreed upon by the participating physicians of thisclinical steering committee. They are specific to this group.The information provided in this document is in no way fully comprehensive.<strong>Pathways</strong> may not be appropriate for use in all circumstances, nor are they asubstitute for the practitioner’s experience and judgment. Their applicability mustbe assessed by the responsible practitioner in light of relevant circumstancespresented by individual patients. Optimal treatment for every individual patientshould be specifically prescribed by the patient’s treating physician. The viewsexpressed in these clinical pathways are those of the authors and do notnecessarily reflect policies and/or official positions of <strong>ION</strong> <strong>Solutions</strong>. As aPractitioner you acknowledge that your use of any of the clinical pathwaysprovided to you is based solely upon your independent clinical judgment, andneither <strong>ION</strong> <strong>Solutions</strong> nor the physicians who participated in the clinical steeringcommittee are liable for decisions made or actions taken by following thesepathways or any of the information contained herein.Page 39 of 39© 2013 by <strong>ION</strong> <strong>Solutions</strong>. All rights reserved

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