Philippine Society of Medical Oncology

Transcription

1 Philippine Society of Medical Oncology Unit 1418, 14/F, orth Tower, Cathedral Heights Bldg., St. Luke s Medical Center E. Rodriguez Sr. Avenue, Quezon City 1099, Philippines Telefax: (632) / local 5318 Governing Council Officers President Vice President Secretary Treasurer Immediate Past President Jasmin V. Reyes-Igama, M.D. Gerardo H. Cornelio, M.D. Maria Belen E. Tamayo, M.D. Agnes S. Evangelista-Gorospe, M.D. Gracieux. Fernando, M.D. Council Members Adonis A. Guancia, M.D. Dennis M. Tudtud, M.D. Ma. oemi L. Alsay-Uy, M.D. Advisory Council Antonio H. Villalon, M.D. Valorie F. Chan, M.D. Corazon A. gelangel, M.D.

2 cpm 8 TH editio The following practice guidelines are the top two cancers in the Philippines. Lung Cancer, followed by Breast Cancer. These guidelines were adapted from the CC (ational Comprehensive Cancer etwork) and was written and reviewed by the following: Medical Oncology Fellows in training Philippine General Hospital Dr. Jose R. Reyes Memorial Medical Center St. Luke's Medical Center Sto Tomas University Hospital Veterans Memorial Medical Center PSMO Governing Council Medical Oncology Consultants The Philippine Society of Medical Oncology, is presently in consultation with other societies dealing with cancer management. Thus we hope the next edition will contain a consensus of practice guidelines, agreed upon by all societies concerned, and to include all the Top Ten cancers in the Philippines. Jasmin V. Reyes-Igama, M.D. PSMO President 310

3 CPM 8 TH EDITIO Algorithm for Breast Cancer 1 breast cancer Breast CA Suspect (A) 2 Open biopsy (B) (+) Cancer? (C) Refer Stage (D) Stage O? LCIS? (E) Observation DCIS Lumpectomy with nodal sampling or MRM ER/PR +? (F) Hormonal Treatment Observe Stage I or II? Go to Fig. C Breast Conservation or MRM (G) Go to Fig. B Figure A 311

4 breast cancer cpm 8 TH editio Ax L+? (H) (+) margin ER/PR+? chemotherapy or (+) L? Radiotherapy (I) (F) + Hormonal treatment Pre-menopausal? chemotherapy Observe Menopausal (+) margin or (+) L? Radiotherapy chemotherapy ± Hormonal treatment Observe Go to #10 14 Tumor size <0.5 cm or cm or with favorable prognostic factors? 15 Go to #2 Observe Figure B 312

5 CPM 8 TH EDITIO breast cancer Stage III? Operable? MRM ER/PR+? (F) Chemotherapy ± Hormonal 6 7 eoadjuvant Chemotherapy (J) 8 RT to breast and regional nodes Chemotherapy with RT 9 10 Chemotherapy RT to breast and regional nodes Stage IV (K) Palliative Surgery (F) Palliative Chemotherapy/ Hormonal Therapy or BSC Palliative Radiotherapy or Best Supportive Care (BSC) Figure C 313

6 breast cancer Management of Breast Cancer cpm 8 TH editio The management of breast cancer must be multidisciplinary, interdisciplinary, with each discipline respecting the specialty expertise of the other, all for the benefit of the cancer patient. (A) Most breast cancer (hard, painless, movable, then becomes fixed to the chest wall/skin, with/without nipple retraction) are found by palpation by the patient, her partner or her physician. As tumor site increases, the likelihood that distant metastasis has taken place rises. It is better to detect and treat early (asymptomatic <1 cm diameter tumor size). Mammography can detect very early <1 cm tumor mass and hence effective in screening. (B) If total mastectomy is anticipated, it is best to confirm the diagnosis with open biopsy. For preliminary screens, FAB cytology is done. A (-) FAB should not dissuade the surgeon from excision biopsy if a discrete lump is present, particularly if there is high clinical suspicion of cancer. 315 Mammography can be done to localize areas with high probability of cancer aiding direction of FAB. Review of slides is done to verify presence of cancer for those patients already with biopsy slides. (C) Majority of breast cancer are invasive ductal carcinoma. Three major cancer types are: noninvasive (intraductal and lobular), invasive, and Paget's disease of the nipple. Poor prognosis types are atypical medullary and not otherwise specified. Other histopathologic findings that correlate with poor prognosis are low nuclear grade and presence of tubule formation. For treatment purposes, breast cancer may be divided into: a. Pure non-invasive carcinoma (Stage 0) i. ductal carcinoma (Stage 0) ii. lobular carcinoma in situ (LCIS) b. Operable locoregional invasive carcinoma (Stage I, II and some stage IIIA) c. Inoperable locoregional invasive carcinoma (Stage IIIB, IIIC and some stage IIIA tumors) d. Metastatic or recurrent carcinoma (Stage IV) (D) Staging considerations: History and PE, and at a minimum alkaline phosphatase, chest x-ray, abdominal ultrasound are done for baseline. Bone scan is indicated if the patient has symptoms related to bone or if there is elevated alkaline phosphatase level. CT scan of whole abdomen is indicated if abdominal ultrasound is inconclusive but there ae symptoms referable to the abdominal organs. At a minimum baseline CBC, creatinine, and ECG are done in preparation for treatment. PET scan can be an option to determine presence of metastatic sites highly suspected but not shown by CT scan/bone scan. For brain metastasis suspect, MRI may be the better option compared to CT scan. (E) The goal of treatment of in-situ carcinoma is either preventing the occurrence of invasive disease or diagnosing the invasive component when still localized to the breast. Observation alone is the preferred option for women diagnosed with LCIS because their risk of developing invasive carcinoma is low. Bilateral mastectomy may be considered in special circumstances. Tamoxifen treatment may be considered in women with DCIS treated with breast conserving therapy, especially in those with ER(+) DCIS treated with mastectomy. (F) Fresh surgical breast mass specimen must be routinely taken at FIRST surgery for ER/PR assay and level of HER-2/neu expression, needed to plan drug treatment of patient. For stage IV or for those cases not previously performed, it is best to determine even on just the excision biopsy specimen the ER/PR and HER-2 status. Hormonal therapy has been shown to reduce overall tumor recurrence and mortality in ER(+) women. Tamoxifen or an aromatase inhibitor agent is the usual hormonotherapy drug. The best responder would be an ER(+)/PR(+) patient; for those premenopausal, tamoxifen can be given; for those post-menopausal, tamoxifen or aromatase inhibitor can be given. For those ER(+)/PR(-), the PR(-) status may be a marker for growth factor overexpression (Her-2 overexpression) and this subgroup of postmenopausal patients may be best started on aromatase inhibitors. HER-2-neu overexpression denotes an aggressive

7 CPM 8 TH EDITIO cancer, resistance to CMF but responsiveness to anti-her-2-neu immunotherapy (trastuzumab). A combination of HER-2-neu ++/PR(-) connotes resistance to CMF-based regimen and tamoxifen. (G) The purpose of surgery is to remove the local and regional disease. A number of randomized trials document that in the majority of women with Stage I and II invasive breast CA, mastectomy with axillary dissection versus breast conserving therapy with lumpectomy, axillary dissection and breast irradiation (breast conserving therapy) are medically equivalent primary therapeutic options. MRM still remains the better option for clinical settings with low patient follow-up rates or low resource settings. Surgical management is the responsibility of the surgical oncologist. (H) For high risk patients with 4 (+)L and (-)ER or for those premenopausal and (-)L or with HER-2-neu over expression, anthracycline-containing adjuvant chemotherapy is given. Otherwise, CMF can be given, particularly for elderly and or patients with heart disease; taxanes can also be given particularly for young, AL(+) 0-3, aggressive and ER/PR(-) tumors. (I) If adjuvant chemotherapy is indicated, RT should be given after chemotherapy is completed. Radiotherapy is the responsibility of the radiation oncologist. breast cancer IIA and IIB tumors and T 3 1 M 0 tumors should be considered for women who meet the criteria for breast conserving therapy except for size. (K) Metastatic sites for breast cancer are usually the regional Ls, skin, lung, liver, bone, brain, etc. Stage IV breast cancer can be those with: 1. 'operable-like' breast mass but with distant metastasis wherein simple mastectomy followed by radiotherapy of target breast and regional Ls sites and symptomatic metastatic sites plus chemotherapy/hormonotherapy, OR wherein radiotherapy to target breast lesion/other symptomatic metastatic sites plus chemotherapy/hormonotherapy can be done, 2. 'inoperable-like' breast mass (adhered, ulcerated, etc) with distant metastasis, wherein toilette mastectomy can be done with chemotherapy/hormonotherapy or radiotherapy or best supportive care. Surgery, chemotherapy, radiotherapy procedures in Stage IV disease are all palliative in goal, although several patients can respond very well to chemotherapy ± radiotherapy and have significantly long time to disease progression interval. Best supportive care mainly includes management of nutrition, pain, infection, psychological well-being, nursing and rehabilitative care, and other pertinent quality of life patient care. It was hoped that post-op RT could prevent locoregional recurrence and improve disease-free and overall survival. It is now evident, however, that this has not occurred to the degree hoped for, probably because remaining tumor burden is too great. Hence, adjuvant systemic chemotherapy is given. More common chemotherapeutic drugs used currently in breast cancer management (neoadjuvant, adjuvant, or palliative setting) are doxorubicin and the other anthracyclines, cyclophosphamide, fluorouracil, taxanes, navelbine, capecitabine, gemcitabine, methotrexate, vincristine, mitomycin-c, carboplatin, trastuzumab. Drug management (from hormonotherapy to gene therapy in the adjuvant to palliative setting) is the responsibility of the medical oncologist who does the planning, the administration, and the monitoring of drug therapeutic and safety effects. (J) Preoperative chemotherapy for large clinical Stage 316

8 breast cancer Drugs Mentioned in the Treatment Guideline cpm 8 TH editio This index lists drugs/drug classifications mentioned in the treatment guideline. Prescribing information of these drugs can be found in the PPD reference systems. Cytotoxic Drugs Alkylating Agents Cyclophosphamide Cytoxan Melphalan Alkeran Antimetabolites 5-Fluorouracil Biomedis Fluorouracil Fluracedyl Fluroblastin Uflahex Capecitabine Xeloda Methotrexate Biomedis Methotrexate Emthexate Hextrate Pfizer Methotrexate Inj. Tegafur/Uracil UFT Cytotoxic Antibiotics Doxorubicin HCl Adriblastina RD Biomedis Doxorubicin HCl Caelyx Pfizer Doxorubicin HCl Inj Pharmachemie Doxorubicin Epirubicin HCl Pharmorubicin Mitomycin C Kyowa Mitomycin-C Mitotic Inhibitors Docetaxel Taxotere Vincristine sulfate Biomedis Vincristine Sulfate evexitin Pfizer Vincristine Injection Pharmachemie Vincristine Other Cytotoxics Carboplatin Biovinate Crobextin Paraplatin Gemcitabine HCl Gemzar Mitoxantrone Domitrone Paclitaxel Taxol 317 Hormones and Antagonists in Malignant Diseases Anastrozole Arimidex Goserelin acetate Zoladex Letrozole Femara Leuprorelin acetate Luprolex Megestrol acetate Megace Pharmachemie Megestrol Acetate Tamoxifen citrate Cox Tamoxifen Drugmaker's Biotech Tamoxifen Fenahex Kessar olvadex/olvadex-d Tamoplex Zitazonium Immunosuppressants Exemestane Aromasin Others Trastuzumab Herceptin

9 CPM 8 TH EDITIO Algorithm for the Management of Lung Cancer 1 2 Lung CA Suspect (A) Chest X-ray PAL (B) o Mass? 9 Centrally located? Peripheral location? 13 Enlarged neck nodes? 15 Pleural effusion? Highly suspect cancer? o other CT Scan o mass? CA site? (C) 8 10 Manage by case. Refer Bronchoscopy with biopsy or cytology (D) 12 Percutaneous FAB (E) Biopsy Thoracentesis with cytology (F) 18 Radiotherapy Go to Fig. 1a Go to Fig. 1a Go to Fig. 1a Go to Fig. 1a Go to # 9 Close follow up. Refer LUG cancer Refer Figure 1 319

10 LUG cancer cpm 8 TH editio o cancer? (G) Highly suspect cancer? Radiotherapy 4 Refer 5 6 SCLC? Go to Figure 1b Stage (H) T 1 T 2 0 M 0? ot Operable? Rt and/or Chemotherapy 10 Lobectomy (J) 11 Rt (K) and/or Chemotherapy (L) T 3 T M 0? Metastatic Palliative chemotherapy and or Rt 13 Chemotherapy ± Rt Figure 1a 320

11 CPM 8 TH EDITIO 1 LUG cancer SCLC 2 3 Stage (I) Stage I? 4 5 Operable? Surgery 6 +margins? 7 Rt 8 Rt 9 Stage II/III? 10 Operable? Surgery Close follow up Rt + Chemo Resectable? Surgery Stage IV Chemo ± Rt Single site mets? Operable? Palliative treatment Chemo ± Rt Multiple Chemo/Rt 24 Palliative Treatment Figure 1b 321

12 LUG cancer The management of lung cancer must be multi-disciplinary and interdisciplinary, with each discipline respecting the specialty expertise of the other, all for the benefit of the cancer patient. (A) A change in pulmonary habits is the most significant sign of lung cancer. Coughs, chest pain, rust colored-streaked sputum, hemoptysis, hoarseness, weight loss, and dyspnea are common symptoms of lung cancer. (B) Postero-anterior and lateral chest films are the most valuable first tolls to establish the diagnosis when there is clinical suspicion of lung cancer. (C) Asymptomatic smaller tumors can be detected by the CT scan. For lung cancer suspect, do CT scan of chest, upper abdomen and adrenal glands. CT scan is also the most useful of all modalities for determining the characteristics of T and in the thorax and M in the brain and liver. (D) Bronchoscopy yields (+) histology only if the lung cancer is centrally located or has invaded centrally. Cytological studies include sputum and bronchial washing exams by Papaniculao technique. (E) Percutaneous needle biopsy guided by fluoroscopy or CT scan gives accurate cytologic diagnosis from peripheral lung lesions and also from liver/bone metastatic lesions. (F) Pleural fluid can undergo cytologic exam when pleural effusion is the presenting symptomatology. (G) There are 2 major histological types, whose management differ accordingly: 1) small cell anaplastic carcinoma (SCLC)- tends to be disseminated at diagnosis; rapidly growing, 2) on-small cell carcinoma (SCLC)- slow growing; with three cell types: a) epidermoid carcinoma - most common centrally located, b) adenocarcinoma - tends to be peripherally located, c) large cell anaplastic carcinoma - similar to adenocarcinoma in metastatic pattern. 322 For both SCLC and SCLC, staging work up includes CT scan of chest, upper abdomen and adrenal glands (if not yet done in diagnostic work up), ultrasound of the liver (if upper abdomen CT scan was not done), brain and bone scans (if symptomatic). cpm 8 TH editio (H) SCLC Stage: 1. Limited disease - confined to lung and regional lymph nodes. 2. Extensive disease - denotes metastasis outside lung and regional lymph nodes. (I) SCLC stage by TM classification A. TM a. T is carcinoma in situ b. T 1 <3 cm tumor size not involving the visceral pleura c. T 2 >3 cm tumor size, >2cm from the carina, (+) visceral i. pleural involvement, partial atelectasis d. T 3 tumor involves the chest wall, diaphragm, mediastinum i. pleura or parietal pericardium, <2 cm from the carina, complete atelectasis of either lung e. T 4 tumor involves the mediastinum, heart, trachea, i. carina, vertebral body; presence of malignant pleural/pericardial effusion; presence of satellite nodule/tumor f. 0 o spread to lymph nodes (L) g. 1 Spread to L within the lungs, ipsilateral hilar Ls h. 2 Spread to subcarinal or ipsilateral mediastinal Ls i. 3 Spread to cervical Ls or contralateral hilar and i. mediastinal Ls j. M 0 o distant spread k. M 1 Spread to distant organs, to other lobes of the i. lungs or to Ls further than those mentioned in stage B. STAGE a. 0 - Tis0M0 b. IA - T10M0 c. IB - T20M0 d. IIA - T11M0 e. IIB - T21M0,T30M0 f. IIIA - T1-T32M0,T31M0 g. IIIB - AnyT3M0, T4AnyM0 h. IVB - AnyT Any M1 (J) In SCLC T1-20M0 and SCLC Stage I and II, surgery is done to achieve complete tumor resection and avoid an exploratory thoracotomy or an incomplete surgical resection. The choice of surgical procedure - lobectomy, pneumonectomy, segmental or sleeve

13 CPM 8 TH EDITIO resection - depends on disease extent and patient's functional status. Here, surgery may not be done if with medical contraindications. The presence of distant metastases or extrahepatic metastasis is indicative of inoperability and a surgical procedure is an absolute contraindication. Surgical management is the responsibility of the surgical oncologist and or the thoracic surgeon. LUG cancer (K) Irradiation is used to achieve: 1. Definitive irradiation of localized lung cancer 2. As part of a combined treatment approach 3. Palliation of symptoms Radiotherapy can be given in combination with chemotherapy if a patient is assessed (age, ECOG performance status, co-morbidities, preference) to be able to receive combination modality of treatment. Radiotherapy is the responsibility of the Radiation Oncologist. (L) In SCLC, combination chemotherapy is the treatment of choice for all stages. In SCLC, chemotherapy is currently restricted to recurrent or metastatic disease and for palliation of inoperable symptomatic patients whose disease is beyond radiotherapy control. Recent data also suggested benefits for Stage III disease after surgery or radiotherapy. eoadjuvant chemotherapy is reported to be promising due to better staging procedures and use of cisplatin-containing regimens. Drug therapy for cancer is the responsibility of the Medical Oncologist. Initial work up prior to any treatment include baseline CBC, creatinine, serum electrolytes, LDH. 323

14 LUG cancer Drugs Mentioned in the Treatment Guideline cpm 8 TH editio This index lists drugs/drug classifications mentioned in the treatment guideline. Prescribing information of these drugs can be found in PPD reference systems. Cytotoxic Drugs Antimetabolites Methotrexate Biomedis Methotrexate Hextrate Tegafur/Uracil UFT Cytotoxic Antibiotics Doxorubicin HCl Adriblastina RD Biomedis Doxorubicin HCl Pfizer Doxorubicin HCl Inj Pharmachemie Doxorubicin Mitotic Inhibitors Docetaxel Taxotere Etoposide Lastet Pfizer Etoposide Posid Topresid Vepesid Vincristine sulfate Biomedis Vincristine Sulfate evexitin Pfizer Vincristine Inj Pharmachemie Vincristine Other Cytotoxics Carboplatin Crobextin Paraplatin Cisplatin Ciplexal ippon Kayaku Cisplatin Platamine Gemcitabine HCl Gemzar Paclitaxel Taxol Others Geftinib Iressa 324