The major features of this chapter are the clinical aspects of cancer, including etiology, prevention, staging, diagnosis, and treatment of common cancers, as well as recognition and management of complications from cancer.
Etiology
Cancer is the second most common cause of death in the United States. In 2023, an estimated 1,958,310 cases of cancer were diagnosed, and 609,820 persons died of cancer. Table 41-1. Estimated 0 Most Common Cancer Cases in the United States in Males and Females (All Races) lists the 10 leading cancer types in men and women by site. However, death rates from cancers are declining. Compared with the 1991 overall cancer death rate of 215 per 100,000 population, the 2016-2020 rate of 149.4 per 100,000 represents a 31% reduction in the overall cancer death rate. Importantly, death rates have declined in all four of the most common cancer types (prostate, breast, lung, and colorectum). Reductions in cancer mortality reflect successful implementation of a broad strategy of prevention, detection, and treatment. Due to these improvements, the number of cancer survivors is increasing. In 2022, an estimated 18.1 million people in the United States were alive in whom cancer had been previously diagnosed, approximately 5.4% of the population.
Table 41-1. Estimated 10 most common cancer cases in the United States in males and females (all races).| Rank | Males | Females |
|---|---|---|
| Total Cases [N] = 1,010,310 (100 percent) | Total Cases [N] = 948,000 (100 percent) | |
| 1 | Prostate 288,300 (29) | Breast 297,790 (31) |
| 2 | Lung and bronchus 117,550 (12) | Lung and bronchus 120,790 (13) |
| 3 | Colon and rectum 81,860 (8) | Colon and rectum 71,160 (8) |
| 4 | Urinary bladder 62,420 (6) | Uterine corpus 66,200 (7) |
| 5 | Melanoma 58,120 (6) | Melanoma 39,490 (4) |
| 6 | Kidney and renal pelvis 52,360 (5) | Non-Hodgkin lymphoma 35,670 (4) |
| 7 | Non-Hodgkin lymphoma 44,880 (4) | Thyroid 31,180 (3) |
| 8 | Oral cavity and pharynx 39,290 (4) | Pancreas 30,920 (3) |
| 9 | Leukemia 35,670 (4) | Kidney and renal pelvis 29,440 (3) |
| 10 | Pancreas 33,130 (3) | Leukemia 23,940 (3) |
| Other sites 196,730 (20) | Other sites 201,420 (21) |
Modifiable Risk Factors
Tobacco use is the most common preventable cause of cancer death; at least 30% of all cancer deaths in the United States are directly linked to tobacco use. Clear evidence links tobacco use to at least 12 cancers. The most dramatic link is with lung cancer; greater than 80% of lung cancer deaths are attributable to smoking. Remarkably, almost 10% of long-term survivors of a tobacco-related cancer continue to use tobacco products, increasing their risk of yet another cancer.
In 2021, the United States Department of Health and Human Services reported that 19% of adults in the United States were active tobacco users, a reduction from the 1955 peak of 57% for men and the 1965 peak of 34% for women. Cigarettes are the most common form of tobacco used in the United States, but among US youth, electronic cigarettes are the most popular form. Electronic cigarette aerosol can contain harmful substances, including nicotine, heavy metals, volatile organic compounds, and carcinogenic substances. From the Annual National Youth Tobacco Survey, the percent of middle and high school students in the United States who used e-cigarettes in 2022-2023 was 10%, a decrease from 14.1% the year prior.
Tobacco cessation directed toward the individual should start with clinician counseling. Simple, concise advice from a clinician can yield cessation rates of 10-20%. Additive strategies include more intensive counseling; nicotine replacement therapy with patches, gum, lozenges, or inhalers; and prescription medication with bupropion or varenicline (see Part 1).
For those Americans who do not use tobacco, the most modifiable cancer risk factors are nutrition and physical activity. Prudent recommendations to reduce cancer risk are to (1) avoid tobacco; (2) be physically active; (3) maintain a healthy weight; (4) consume a diet rich in fruits, vegetables, and whole grains; (5) lower consumption of saturated and trans dietary fats; (6) limit alcohol use; and (7) avoid excess sun exposure.
Another modifiable cancer risk factor is radiation from radiographic studies. A 2009 study reported that the use of CT in diagnostic algorithms exposes individuals to significant radiation doses that may increase their lifetime risk of cancer. Both standardization of CT radiation doses and limiting testing have been important steps in minimizing this risk. The American Society of Hematology and American Society of Clinical Oncology have guidelines, inspired by the American Board of Internal Medicine Foundation's "Choosing Wisely" campaign, for limiting radiographic testing, particularly when used in surveillance for treated patients with cancer.
American Cancer Society. Cancer Facts & Figures 2023. http://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/2023-cancer-facts-figures.html KleinWMPet al. Alcohol and cancer risk: clinical and research implications. JAMA. 2020;323:23. [PMID: 31834355] Office of Disease Prevention and Health Promotion. Healthy People 2030. Tobacco use objectives: reduce current tobacco use in adults-TU-01. http://health.gov/healthypeople/objectives-and-data/browse-objectives/tobacco-use/reduce-current-tobacco-use-adults-tu-01. SiegelRLet al. Cancer statistics, 2024. CA Cancer J Clin. 2024;74:12. [PMID: 38230766] Erratum in: CA Cancer J Clin. 2024;74:203. [PMID: 38363123] US Food and Drug Administration. Results from the Annual National Youth Tobacco Survey. http://www.fda.gov/tobacco-products/youth-and-tobacco/results-annual-national-youth-tobacco-survey#Findings%20on%20Youth%20Use%20for%20E-Cigarette%20Products. |
Staging
The Tumor, Node, Metastasis (TNM) system is the commonly used classification to stage cancer. Staging is important not only because it correlates with the patient's long-term survival but also because it is used to determine treatment strategies.
The most used staging system at the time of a cancer diagnosis is the TNM system. Rules for staging for individual cancers are established and published by the American Joint Committee on Cancer (AJCC). The elements used for staging are tumor location, size, and level of invasion (T); absence or presence and extent of nodal metastases (N); and absence or presence of systemic metastases (M). Once the TNM designations have been determined, an overall stage (I, II, III, or IV) is assigned. Clinical staging utilizes physical examination, laboratory and imaging tests as well as results from biopsies; pathologic staging relies on the results from surgery. The AJCC Cancer Staging Manual 8th edition was implemented in the United States in January 2018. Other classifications may be used for some cancers such as the Ann Arbor staging system for lymphomas.
Certain characteristics of cancers, not reflected in the TNM stage, may be used to indicate prognosis and guide treatment. Pathologic features seen on routine histologic examination for some cancers are very important; examples include the Gleason score for prostate cancer, HPV status of oropharyngeal cancer, and grade of sarcomas. Cancer specimens should also be sent for molecular diagnostic testing. Programmed death-ligand 1 (PD-L1) expression testing should be sent for certain cancers (including lung, head/neck, esophageal cancers).
KumarAet al. Long-term survival of American Joint Committee on Cancer 8th Edition staging descriptors for clinical M1a non-small cell lung cancer. Chest. 2024;165:725. [PMID: 37544427] |
Treatment
See Primary Cancer Treatment section below. Table 41-2. Treatment Choices for Cancers Responsive to Systemic Agents (Listed in Alphabetical Order) outlines treatment choices by cancer type for those responsive to systemic agents, and Table 41-3. Common Cancer Therapeutic Agents (Listed in Alphabetical Order Within Classes) provides a listing of common chemotherapeutic agents.
Table 41-2. Treatment choices for cancers responsive to systemic agents (listed in alphabetical order).| Diagnosis | Initial Treatment |
|---|---|
| Acute lymphoblastic leukemia (ALL) | Induction combination chemotherapy (Philadelphia chromosome-positive): Cyclophosphamide, vincristine, doxorubicin/daunorubicin, dexamethasone (hyper-CVAD) alternating with cytarabine, methotrexate; add imatinib or dasatinib or nilotinib Induction combination chemotherapy (Philadelphia chromosome-negative): Daunorubicin, vincristine, prednisone, pegaspargase, cyclophosphamide; or hyper-CVAD alternating with methotrexate and cytarabine |
| Acute myeloid leukemia (AML) | Induction combination therapy: Cytarabine with daunorubicin or idarubicin, with gemtuzumab ozogamicin (CD33-positive), or with midostaurin or quizartinib (FLT3-mutated) Liposomal encapsulation of cytarabine and daunorubicin (therapy-related or myelodysplasia-related changes for ≥ 60 y) Alternative therapy for intensive induction ineligible: Azacitidine or decitabine with venetoclax; or Ivosidenib (IDH1 mutation); or Enasidenib (IDH2 mutation) |
| Adrenal cancer | Cisplatin or carboplatin with etoposide, with or without doxorubicin, with or without mitotane |
| Anal cancer | Mitomycin with 5-fluorouracil or capecitabine with radiation Carboplatin, paclitaxel with or without radiation therapy |
| Bladder cancer | Combination chemotherapy: Gemcitabine, cisplatin followed by avelumab maintenance, or Methotrexate, vinblastine, doxorubicin, cisplatin (MVAC), or Pembrolizumab, pembrolizumab and enfortumab vedotin-ejfv or gemcitabine plus carboplatin (cisplatin-ineligible) |
| Brain cancer ( glioblastoma) | Single-agent chemotherapy with radiation therapy: Temozolomide |
| Breast cancer | Adjuvant hormone therapy:Premenopausal: Tamoxifen Postmenopausal: Aromatase inhibitors (anastrozole, letrozole, exemestane) Adjuvant therapy (HER2 negative): Doxorubicin, cyclophosphamide, followed by paclitaxel, or Docetaxel, cyclophosphamide, or Olaparib if germline BRCA1/2 pathogenic variants, or High-risk triple-negative-preoperative pembrolizumab/carboplatin/paclitaxel, followed by pembrolizumab/cyclophosphamide/doxorubicin or epirubicin, followed by adjuvant pembrolizumab Adjuvant therapy (HER2 positive): Docetaxel, carboplatin, trastuzumab with or without pertuzumab, or Paclitaxel, trastuzumab |
| Carcinoid | Octreotide LAR or lanreotide or everolimus or lutetium (Lu)-177 dotatate |
| Cervical cancer | With radiation: Cisplatin or carboplatin Combination chemotherapy: Cisplatin or carboplatin, paclitaxel, with or without bevacizumab, add pembrolizumab for PD-L1-positive tumors |
| Chronic lymphocytic leukemia (CLL) | Venetoclax with obinutuzumab, or acalabrutinib with or without obinutuzumab, or zanubrutinib |
| Chronic myeloid leukemia (CML) | Nilotinib or dasatinib or imatinib or bosutinib |
| Colon cancer | 5-Fluorouracil, leucovorin, oxaliplatin (FOLFOX) with or without bevacizumab, or Capecitabine, oxaliplatin (CAPEOX) with or without bevacizumab, or 5-Fluorouracil, leucovorin, irinotecan (FOLFIRI) with or without bevacizumab 5-Fluorouracil, leucovorin, oxaliplatin, irinotecan (FOLFIRINOX) with or without bevacizumab Cetuximab or panitumumab added to FOLFOX or FOLFIRI for KRAS/NRAS/BRAF wild-type and left-sided cancers Capecitabine or 5-fluorouracil/leucovorin with or without bevacizumab Pembrolizumab, dostarlimab-gxly; or nivolumab with or without ipilimumab (deficient mismatch repair [dMMR]/high-level microsatellite instability [MSI-H]) |
| Esophageal and esophagogastric junction cancer | Cisplatin, 5-fluorouracil or capecitabine, or Paclitaxel, carboplatin, or Oxaliplatin, 5-fluorouracil or capecitabine, or 5-Fluorouracil, leucovorin, oxaliplatin, docetaxel (FLOT) Add trastuzumab for HER2-overexpressing metastatic adenocarcinoma, or 5- Fluorouracil, leucovorin, oxaliplatin, nivolumab Nivolumab and ipilimumab for squamous cell carcinoma |
| Gestational trophoblastic neoplasia | Single-agent chemotherapy: Methotrexate or dactinomycin for low-risk disease Combination chemotherapy: Etoposide, methotrexate, dactinomycin/ cyclophosphamide, vincristine (EMA/CO) for high-risk disease Etoposide, methotrexate, dactinomycin/etoposide,cisplatin (EMA/EP or EP/EMA) |
| Hairy cell leukemia | Cladribine with or without rituximab1 or pentostatin |
| Head and neck cancer | Cisplatin with radiation therapy, or Carboplatin with 5-fluorouracil with radiation therapy, or Docetaxel, cisplatin, 5-fluorouracil, or Pembrolizumab (PD-L1 ≥ 1%), or Pembrolizumab/cisplatin or carboplatin/5-fluorouracil |
| Hepatocellular cancer | Atezolizumab with bevacizumab Tremelimumab-actl with durvalumab |
| Hodgkin lymphoma | Doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD), or Brentuximab vedotin (BV) with doxorubicin, vinblastine, dacarbazine (AVD) Bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone (BEACOPP) |
| Kaposi sarcoma | Liposomal doxorubicin |
| Kidney (renal cell) cancer | Clear cell histology: Axitinib or lenvatinib plus pembrolizumab, or ipilimumab plus nivolumab, or cabozantinib with or without nivolumab Non-clear cell histology: Cabozantinib |
| Melanoma | Nivolumab with ipilimumab or relatlimab-rmbw; or pembrolizumab, or nivolumab Dabrafenib/trametinib or vemurafenib/cobimetinib or encorafenib/binimetinib (BRAF mutation) |
| Mesothelioma | Cisplatin or carboplatin/pemetrexed with or without bevacizumab, or Nivolumab with ipilimumab |
| Multiple myeloma | Combination chemotherapy (transplant candidates): Bortezomib, dexamethasone, lenalidomide Followed by autologous or mini-allogeneic stem cell transplantation Combination chemotherapy (non-transplant candidates): Bortezomib, lenalidomide, dexamethasone, or Daratumumab, lenalidomide, dexamethasone |
| Neuroblastoma | Combination chemotherapy: Cyclophosphamide, doxorubicin, cisplatin, etoposide |
| Non-Hodgkin lymphoma (intermediate and high-grade) | Cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab1 (CHOP-R), or Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab1 (dose-adjusted R-EPOCH) (for double-/triple-hit) |
| Non-Hodgkin lymphoma (low-grade) | Bendamustine plus obinutuzumab or rituximab1 , or Cyclophosphamide, vincristine, doxorubicin, prednisone, obinutuzumab or rituximab1 or Cyclophosphamide, vincristine, prednisone,with binutuzumab or rituximab1 or Lenalidomide, rituximab1 |
| Non-small cell lung cancer | Combination therapy: Cisplatin, etoposide, or Paclitaxel, carboplatin, or Cisplatin, gemcitabine or docetaxel (squamous histology), or Cisplatin, pemetrexed (nonsquamous histology), or Carboplatin, albumin-bound paclitaxel, or Dabrafenib/trametinib (BRAF V600E mutation), or Carboplatin or cisplatin/pemetrexed/pembrolizumab (nonsquamous); carboplatin/paclitaxel or albumin-bound paclitaxel/pembrolizumab (squamous) Nivolumab/ipilimumab Single-agent therapy: Erlotinib, gefitinib, osimertinib, afatinib, or dacomitinib (EGFR mutation positive) Sotorasib or adagrasib (KRAS G12C mutation positive) Crizotinib, alectinib, ceritinib, lorlatinib, or brigatinib (ALK rearrangement) Ceritinib, crizotinib, or entrectinib (ROS1 rearrangement) Larotrectinib or entrectinib (NTRK gene fusion positive) Capmatinib or tepotinib (MET exon 14 skipping mutation) Selpercatinib or pralsetinib (RET rearrangement positive) Pembrolizumab, or atezolizumab, or cemiplimab-rwlc (PD-L1 ≥ 50%) |
| Osteosarcoma | Cisplatin with doxorubicin, or Methotrexate, doxorubicin, cisplatin (MAP) |
| Ovarian cancer | Paclitaxel, carboplatin, with or without bevacizumab, or 5-Fluorouracil/leucovorin or capecitabine, oxaliplatin |
| Pancreatic cancer | Combination chemotherapy: Gemcitabine, albumin-bound paclitaxel, or 5-Fluorouracil, leucovorin, irinotecan, oxaliplatin (FOLFIRINOX), or Gemcitabine, capecitabine, or Gemcitabine, cisplatin (for BRCA1/2 or PALB2 mutation) Single-agent chemotherapy: Gemcitabine or capecitabine |
| Polycythemia vera | Phlebotomy or hydroxyurea or aspirin |
| Prostate cancer | Hormone therapy: LH-releasing agonist (leuprolide, goserelin, triptorelin, histrelin) or degarelix with or without an antiandrogen (flutamide, bicalutamide, nilutamide, enzalutamide, apalutamide) or abiraterone Chemotherapy: Docetaxel |
| Rectal cancer | 5-Fluorouracil or capecitabine with radiation, or FOLFOX or CAPEOX |
| Small cell lung cancer | Cisplatin, etoposide (limited stage) with radiation, or Cisplatin or carboplatin, etoposide, atezolizumab or durvalumab (extensive stage) |
| Soft tissue sarcomas | Combination chemotherapy: Doxorubicin, dacarbazine (AD), or Doxorubicin, ifosfamide, mesna (AIM), or Ifosfamide, epirubicin, mesna Single-agent therapy: Imatinib or avapritinib (GI stromal tumors) Doxorubicin or epirubicin or liposomal doxorubicin |
| Stomach (gastric) cancer | 5-Fluorouracil, leucovorin, oxaliplatin, docetaxel (FLOT) (perioperative) 5-Fluorouracil or capecitabine with oxaliplatin or cisplatin Add trastuzumab for HER2-overexpressing adenocarcinomas 5-Fluorouracil or capecitabine, oxaliplatin, nivolumab |
| Testicular cancer | Cisplatin, etoposide (EP), or Bleomycin, etoposide, cisplatin (BEP), or Etoposide, mesna, ifosfamide, cisplatin (VIP) |
| Thyroid cancer | Single-agent therapy: Radioiodine (131 I) or lenvatinib, vandetanib or cabozantinib (medullary thyroid cancer) |
| Uterine cancer | Hormone therapy: Progestins, tamoxifen, aromatase inhibitors Chemotherapy: Cisplatin with radiation Carboplatin, paclitaxel with or without pembrolizumab or dostarlimab-gxly Carboplatin, paclitaxel, trastuzumab (HER2 positive) |
| Waldenstrom macroglobulinemia | Plasmapheresis alone or followed by combination chemotherapy: Ibrutinib with or without rituximab1 Bortezomib, dexamethasone, rituximab1 , or Bendamustine, rituximab1 , or Zanubrutinib |
1 In patients with past hepatitis B virus (HBV) infection, rituximab should be used with anti-HBV agent (eg, entecavir) prophylaxis since HBV reactivation, fulminant hepatitis, and, rarely, death can occur otherwise.
| Chemotherapeutic Agent | Usual Adult Dosage | Adverse Effects |
|---|---|---|
| Alkylating Agents-Nitrogen Mustards | ||
| Bendamustine (Treanda) | 90-120 mg/m2 intravenously every 3-4 weeks | Acute: hypersensitivity, nausea, vomiting Delayed: myelosuppression, rash, pyrexia, fatigue |
| Cyclophosphamide (Cytoxan) | 500-1000 mg/m2 intravenously every 3 weeks; 100 mg/m2 /day orally for 14 days every 4 weeks; various doses | Acute: nausea and vomiting Delayed: myelosuppression, alopecia, hemorrhagic cystitis, cardiotoxicity (high dose) |
| Ifosfamide (Ifex) | 1200 mg/m2 intravenously daily for 5 days every 3 weeks; various doses | Acute: nausea and vomiting Delayed: alopecia, myelosuppression, hemorrhagic cystitis, neurotoxicity |
| Alkylating Agents-Platinum Analogs | ||
| Carboplatin (Paraplatin) | AUC-based dosing use Calvert equation [Dose (mg) = AUC × (GFR + 25)] AUC = 2-7 mg/mL/min every 2-4 weeks | Acute: nausea and vomiting Delayed: myelosuppression, electrolyte disturbances, peripheral neuropathy, nephrotoxicity, hypersensitivity |
| Cisplatin (Platinol) | 50-100 mg/m2 intravenously every 3-4 weeks; 20 mg/m2 /day intravenously for 5 days every 3 weeks; various doses | Acute: nausea and vomiting Delayed: nephrotoxicity, ototoxicity, neurotoxicity, myelosuppression, electrolyte disturbances |
| Oxaliplatin (Eloxatin) | 85-130 mg/m2 intravenously every 2-3 weeks; various doses | Acute: peripheral neuropathy exacerbated by cold, nausea, vomiting, diarrhea Delayed: myelosuppression, elevated transaminases |
| Alkylating Agents-Triazenes | ||
| Dacarbazine (DTIC-Dome) | 375 mg/m2 intravenously on days 1 and 15 every 4 weeks; 900-1000 mg/m2 intravenously over 3-4 days; various doses | Acute: nausea, vomiting, photosensitivity Delayed: myelosuppression, anorexia, hypotension, flu-like syndrome |
| Procarbazine (Matulane) | 60-100 mg/m2 orally for 14 days every 4 weeks; various doses | Acute: nausea and vomiting Delayed: myelosuppression, disulfiram-like reaction, MAO inhibition, rash |
| Temozolomide (Temodar) | 75 mg/m2 orally daily during radiation for 42 days; 150-200 mg/m2 orally for 5 days every 4 weeks; various doses | Acute: nausea, vomiting, constipation Delayed: myelosuppression, fatigue |
| Antimetabolites-Folate Antagonists | ||
| Methotrexate (MTX; Trexall) | Intrathecal: 12 mg High dose: 1000-12,000 mg/m2 intravenously every 2-3 weeks; various doses | Acute: nausea, vomiting, mucositis Delayed: myelosuppression, nephrotoxicity, hepatotoxicity, neurotoxicity, photosensitivity, pulmonary toxicity |
| Pemetrexed (Alimta) | 500 mg/m2 intravenously every 3 weeks | Acute: nausea, vomiting, diarrhea, rash Delayed: myelosuppression, fatigue, mucositis |
| Antimetabolites-Purine Analogs | ||
| Cladribine (Leustatin) | 0.1 mg/kg/day subcutaneously daily for 5 days or 0.09 mg/kg/day intravenously via continuous infusion for 7 days; various doses | Acute: nausea, injection site reaction Delayed: myelosuppression, immunosuppression, fever, fatigue, rash |
| Fludarabine (Fludara) | 25 mg/m2 intravenously for 5 days every 4 weeks; various doses | Acute: fever, nausea, vomiting Delayed: asthenia, myelosuppression, immunosuppression, neurotoxicity, anorexia |
| Pentostatin (Nipent) | 2-4 mg/m2 intravenously every 2-3 weeks | Acute: nausea, vomiting, rash Delayed: myelosuppression, fever, myalgia, immunosuppression, hepatotoxicity, cough |
| Antimetabolites-Pyrimidine Analogs | ||
| Azacitidine (Vidaza) | 75-100 mg/m2 subcutaneously or intravenously for 7 days every 4 weeks | Acute: injection site reaction (subcutaneously), nausea, diarrhea, fever Delayed: myelosuppression, dyspnea, arthralgia |
| Capecitabine (Xeloda) | 1000-1250 mg/m2 orally twice a day for 14 days every 3 weeks | Acute: nausea, vomiting, diarrhea Delayed: hand-foot syndrome, mucositis, hyperbilirubinemia, myelosuppression |
| Cytarabine (Ara-C, Cytosar U) | Standard dose: 100 mg/m2 /day intravenously via continuous infusion for 7 days High dose: 1000-3000 mg/m2 intravenously every 12 hours for 2-6 days | Acute: nausea, vomiting, rash, flu-like syndrome Delayed: myelosuppression High dose: neurotoxicity, ocular toxicities |
| Decitabine (Dacogen) | 15 mg/m2 intravenously every 8 hours for 3 days every 6 weeks; 20 mg/m2 intravenously daily for 5 days | Acute: nausea, vomiting, hyperglycemia Delayed: myelosuppression, fever, fatigue, cough |
| Fluorouracil (Adrucil) | 400 mg/m2 intravenous bolus followed by 2400 mg/m2 intravenously over 46 hours every 2 weeks; 1000 mg/m2 intravenously via continuous infusion for 4-5 days every 3-4 weeks; various doses | Acute: nausea, vomiting, diarrhea Delayed: myelosuppression, hand-foot syndrome, mucositis, photosensitivity, cardiotoxicity (rare) |
| Gemcitabine (Gemzar) | 1000-1250 mg/m2 intravenously on days 1 and 8 every 3 weeks or days 1, 8, 15 every 4 weeks; various doses | Acute: nausea, vomiting, rash, flu-like symptoms, fever, diarrhea Delayed: myelosuppression, edema, elevated transaminases |
| Antimicrotubules-Vinca Alkaloids | ||
| Vinblastine (Velban) | 6 mg/m2 intravenously on days 1 and 15 every 4 weeks; various doses | Acute: constipation Delayed: myelosuppression, alopecia, bone pain, malaise |
| Vincristine (Oncovin) | 0.5-1.4 mg/m2 intravenously every 3 weeks; various doses; maximum single dose usually limited to 2 mg | Acute: constipation, nausea Delayed: peripheral neuropathy, alopecia |
| Antimicrotubules-Taxanes | ||
| Docetaxel (Taxotere) | 60-100 mg/m2 intravenously every 3 weeks | Acute: nausea, vomiting, diarrhea, hypersensitivity, rash Delayed: myelosuppression, asthenia, peripheral neuropathy, alopecia, edema, mucositis |
| Paclitaxel (Taxol) | 135-175 mg/m2 intravenously every 3 weeks; 50-80 mg/m2 intravenously weekly; various doses | Acute: diarrhea, nausea, vomiting, hypersensitivity Delayed: myelosuppression, peripheral neuropathy, alopecia, mucositis, arthralgia |
| Paclitaxel protein-bound (Abraxane) | 100-125 mg/m2 on days 1, 8, 15 every 3-4 weeks; 260 mg/m2 intravenously every 3 weeks | Acute: nausea, vomiting, diarrhea Delayed: myelosuppression, peripheral neuropathy, alopecia, asthenia |
| Enzyme Inhibitors-Anthracyclines | ||
| Daunorubicin (Cerubidine) | 30-60 mg/m2 intravenously for 3 days | Acute: nausea, vomiting, diarrhea, red/orange discoloration of urine, infusion-related reactions (liposomal products) Delayed: myelosuppression, mucositis, alopecia, hand-foot syndrome (liposomal doxorubicin), cardiotoxicity (dose related) |
| Doxorubicin (Adriamycin) | 45-75 mg/m2 intravenously every 3 weeks; various doses | |
| Epirubicin (Ellence) | 60-120 mg/m2 intravenously every 3-4 weeks | |
| Idarubicin (Idamycin) | 10-12 mg/m2 intravenously for 3 days | |
| Liposomal doxorubicin (Doxil, Lipodox) | 20-50 mg/m2 intravenously every 3-4 weeks | |
| Enzyme Inhibitors-Topoisomerase Inhibitors | ||
| Etoposide (Vepesid) | 50-100 mg/m2 intravenously for 3-5 days every 3 weeks | Acute: nausea, vomiting, diarrhea, hypersensitivity, fever, hypotension Delayed: myelosuppression, alopecia, fatigue |
| Irinotecan (Camptosar) | 180 mg/m2 intravenously every other week; various doses | Acute: diarrhea, cholinergic syndrome, nausea, vomiting Delayed: myelosuppression, alopecia, asthenia |
| Hormonal-Antiandrogens | ||
| Apalutamide (Erleada) | 240 mg orally once daily | Acute: fatigue, diarrhea Delayed: arthralgia, hot flashes, falls, peripheral edema, seizure (rare) |
| Bicalutamide (Casodex) | 50-150 mg orally once daily | Acute: none Delayed: hot flashes, back pain, asthenia |
| Darolutamide (Nubeqa) | 600 mg orally twice daily | Acute: none Delayed: fatigue, transaminitis, increased bilirubin, decreased neutrophils, skin rash, seizure (rare) |
| Enzalutamide (Xtandi) | 160 mg orally once daily | Acute: asthenia, diarrhea Delayed: hot flashes, arthralgia, peripheral edema, seizure (rare) |
| Flutamide (Eulexin) | 250 mg orally every 8 hours | Acute: diarrhea Delayed: hot flashes, hepatotoxicity |
| Nilutamide (Nilandron) | 300 mg orally for 30 days, then 150 mg orally once daily | Acute: none Delayed: visual disturbances (impaired adaptation to dark), hot flashes, disulfiram-like reaction |
| Hormonal-Aromatase Inhibitors | ||
| Anastrozole (Arimidex) | 1 mg orally once daily | Acute: nausea Delayed: hot flashes, peripheral edema, asthenia, hypercholesterolemia, arthralgia/myalgia, osteoporosis |
| Exemestane (Aromasin) | 25 mg orally once daily | |
| Letrozole (Femara) | 2.5 mg orally once daily | |
| Hormonal-LHRH Analogs | ||
| Goserelin acetate (Zoladex) | 3.6 mg subcutaneously every month;10.8 mg subcutaneously every 3 months | Acute: injection site discomfort Delayed: hot flashes, tumor flare, edema, decreased libido, erectile dysfunction, osteoporosis |
| Leuprolide (Lupron Depot, Eligard) | 1 month: 7.5 mg intramuscularly or subcutaneously every month 3 month: 22.5 mg intramuscularly or subcutaneously every 3 months 4 month: 30 mg intramuscularly or subcutaneously every 4 months 6 month: 45 mg intramuscularly or subcutaneously every 6 months | |
| Triptorelin pamoate (Trelstar) | 3.75 mg intramuscularly every 4 weeks; 11.25 mg intramuscularly every 12 weeks; 22.5 mg intramuscularly every 24 weeks | |
| Hormonal-LHRH Antagonist | ||
| Degarelix (Firmagon) | 240 mg subcutaneously once, then 80 mg subcutaneously every 28 days | Acute: injection site reaction Delayed: hot flashes, weight gain, elevated transaminases, QT prolongation |
| Relugolix (Orgovyx) | 360 mg orally on day 1, then 120 mg orally once daily | Acute: none Delayed: hot flashes, hyperglycemia, hypertriglyceridemia, elevated transaminases, anemia, QT prolongation |
| Hormonal-Pure Estrogen Receptor Antagonist | ||
| Fulvestrant (Faslodex) | 500 mg intramuscularly on days 1, 15, 29, then monthly | Acute: injection site reaction, nausea Delayed: hot flashes, bone pain, elevated transaminases |
| Hormonal-Selective Estrogen Receptor Modulators | ||
| Tamoxifen (Nolvadex) | 20-40 mg orally once daily | Acute: none Delayed: hot flashes, vaginal discharge, menstrual irregularities, arthralgia |
| Targeted Therapy-Monoclonal Antibodies | ||
| Atezolizumab (Tecentriq) | 840 mg intravenously every 2 weeks or 1200 mg intravenously every 3 weeks or 1,680 mg intravenously every 4 weeks | Acute: infusion-related reaction Delayed: immune-mediated reactions, fatigue, decreased appetite |
| Avelumab (Bavencio) | 800 mg intravenously every 2 weeks | Acute: infusion-related reaction Delayed: immune-mediated reactions, fatigue, decreased appetite |
| Bevacizumab (Avastin) | 5-15 mg/kg intravenously every 2-3 weeks | Acute: infusion-related reaction Delayed: hypertension, proteinuria, wound healing complications, GI perforation, hemorrhage |
| Cemiplimab-rwlc (Libtayo) | 350 mg intravenously every 3 weeks | Acute: infusion-related reaction, nausea, diarrhea Delayed: immune-mediated reactions |
| Cetuximab (Erbitux) | Loading dose 400 mg/m2 intravenously; maintenance dose 250 mg/m2 intravenously weekly | Acute: infusion-related reaction, nausea, diarrhea Delayed: acneiform skin rash, hypomagnesemia, asthenia, paronychial inflammation, dyspnea |
| Daratumumab (Darzalex) | 16 mg/kg intravenously weekly for weeks 1-8, every 2 weeks for weeks 9-24, and every 4 weeks from week 25 until disease progression | Acute: infusion-related reaction, nausea Delayed: myelosuppression, fatigue, upper respiratory tract infection |
| Dostarlimab (Jemperli) | 500 mg intravenously every 3 weeks × 4 doses, followed by 1000 mg intravenously every 6 weeks for dose 5 and beyond | Acute: infusion-related reaction Delayed: immune-mediated reactions, fatigue, decreased appetite |
| Durvalumab (Imfinzi) | Dosing schedules vary by cancer type and patient weight. For example, for those < 30 kg, 20 mg/kg/dose intravenously every 3 weeks cycles 1 to 4, then 20 mg/kg/dose intravenously every 4 weeks cycle 5 and beyond. For those >30 kg, 1500 mg intravenously every 3 weeks cycles 1 to 4, then 1500 mg intravenously every 4 weeks cycles 5 and beyond | Acute: infusion-related reaction Delayed: immune-mediated reactions, fatigue, decreased appetite |
| Ipilimumab (Yervoy) | 1-10 mg/kg intravenously every 3 weeks for a total of four doses | Acute: infusion-related reaction Delayed: immune-related reactions, fatigue, diarrhea, nausea, pruritus |
| Nivolumab (Opdivo) | 240 mg intravenously every 2 weeks or 480 mg every 4 weeks; various doses | Acute: infusion-related reaction, vomiting Delayed: immune-mediated reactions, fatigue, nausea, decreased appetite |
| Obinutuzumab (Gazyva) | Cycle 1: 100 mg intravenously on day 1, 900 mg on day 2, 1000 mg on days 8 and 15 of a 28-day cycle; cycles 2-6: 1000 mg intravenously on day 1; various doses | Acute: infusion-related reaction, TLS Delayed: myelosuppression, pyrexia, cough, musculoskeletal disorder, potential hepatitis B reactivation |
| Panitumumab (Vectibix) | 6 mg/kg intravenously every 2 weeks | Acute: infusion-related reaction, nausea Delayed: acneiform skin rash, hypomagnesemia, asthenia, paronychia, fatigue, dyspnea |
| Pembrolizumab (Keytruda) | 200 mg intravenously every 3 weeks or 400 mg every 6 weeks | Acute: infusion-related reaction, nausea Delayed: immune-mediated reactions, fatigue, cough |
| Pertuzumab (Perjeta) | 840 mg intravenously once followed by 420 mg intravenously every 3 weeks | Acute: infusion-related reaction, diarrhea, nausea Delayed: fatigue, alopecia, neutropenia, rash, peripheral neuropathy, cardiomyopathy |
| Rituximab (Rituxan) | 375 mg/m2 intravenously weekly for 4 weeks, or every 3-4 weeks; various doses | Acute: infusion-related reaction, TLS Delayed: lymphopenia, asthenia, rash, potential hepatitis B reactivation |
| Trastuzumab (Herceptin) | Initial dose 4 mg/kg intravenously, then 2 mg/kg intravenously weekly; or initial dose 8 mg/kg, then 6 mg/kg, intravenously every 3 weeks | Acute: headache, nausea, diarrhea, infusion-related reaction Delayed: myelosuppression, pyrexia, cardiomyopathy, pulmonary toxicity (rare) |
| Targeted Therapy-Kinase Inhibitors | ||
| Acalabrutinib (Calquence) | 100 mg orally every 12 hours | Acute: diarrhea Delayed: myelosuppression, upper respiratory infection, musculoskeletal pain |
| Afatinib (Gilotrif) | 40 mg orally once daily without food | Acute: diarrhea Delayed: acneiform rash, stomatitis, paronychia |
| Alectinib (Alecensa) | 600 mg orally twice daily with food | Acute: none Delayed: myelosuppression, fatigue, edema, myalgia, dyspnea, elevated transaminases |
| Axitinib (Inlyta) | 5-10 mg orally every 12 hours | Acute: diarrhea, nausea, vomiting Delayed: hypertension, fatigue, dysphonia, hand-foot syndrome, elevated transaminases |
| Bosutinib (Bosulif) | 400-600 mg orally once daily with food | Acute: diarrhea, nausea, vomiting Delayed: myelosuppression, rash, abdominal pain, hepatotoxicity, fluid retention |
| Brigatinib (Alunbrig) | 90 mg orally once daily for 7 days then 180 mg orally once daily | Acute: nausea, diarrhea Delayed: increased CPK, hyperglycemia, increased amylase/lipase, hypertension, vision changes, bradycardia, pneumonitis, photosensitivity |
| Capmatinib (Tabrectra) | 400 mg orally twice daily | Acute: nausea, vomiting Delayed: edema, photosensitivity, hepatotoxicity, pneumonitis |
| Ceritinib (Zykadia) | US Dosing: 450 mg orally once daily with food Non-US Dosing: 750 mg orally once daily without food | Acute: diarrhea, nausea, vomiting Delayed: elevated transaminases, abdominal pain, fatigue, decreased appetite |
| Cobimetinib (Cotellic) | 60 mg orally once daily on days 1-21 of a 28-day cycle | Acute: diarrhea, photosensitivity reaction, nausea, vomiting Delayed: myelosuppression, hepatotoxicity, rash, cardiomyopathy (with vemurafenib) |
| Crizotinib (Xalkori) | 250 mg orally twice daily | Acute: nausea, vomiting, diarrhea, constipation Delayed: vision disorder, edema, elevated transaminases, fatigue |
| Dabrafenib (Tafinlar) | 150 mg orally every 12 hours without food | Acute: headache Delayed: hyperkeratosis, fever, hand-foot syndrome, hyperglycemia, hypophosphatemia |
| Dacomitinib (Vizimpro) | 45 mg orally once daily | Acute: diarrhea Delayed: rash, paronychia, mucositis, cough, interstitial lung disease |
| Dasatinib (Sprycel) | 100-180 mg orally once daily | Acute: diarrhea, nausea, vomiting Delayed: myelosuppression, fluid retention, fatigue, dyspnea, musculoskeletal pain, rash |
| Entrectinib (Rozlytrek) | 600 mg orally once daily | Acute: nausea, vomiting, diarrhea Delayed: fatigue, cognitive impairment, HF, potential for birth defects, hepatotoxicity, vision disorder, prolonged QT interval (rare) |
| Erlotinib (Tarceva) | 100 or 150 mg orally once daily without food | Acute: diarrhea, nausea, vomiting Delayed: acneiform skin rash, fatigue, anorexia, dyspnea |
| Everolimus (Afinitor) | 10 mg orally once daily | Acute: mucositis, diarrhea, nausea Delayed: myelosuppression, fatigue, edema, hypercholesterolemia, hypertriglyceridemia, hyperglycemia |
| Gefitinib (Iressa) | 250 mg orally once daily | Acute: diarrhea Delayed: acneiform skin rash |
| Ibrutinib (Imbruvica) | 420 orally once daily | Acute: diarrhea, nausea Delayed: myelosuppression, fatigue, edema, rash, elevated serum creatinine, hemorrhage |
| Imatinib (Gleevec) | 100-800 mg orally once daily with food; various doses | Acute: nausea, vomiting, diarrhea Delayed: edema, muscle cramps, rash, myelosuppression, hepatotoxicity |
| Larotrectinib (Vitrakvi) | 100 mg orally twice daily | Acute: nausea, vomiting, diarrhea Delayed: fatigue, cognitive impairment, potential for birth defects, hepatotoxicity |
| Lenvatinib (Lenvima) | 8-24 mg orally once daily | Acute: hypertension, nausea, vomiting, diarrhea Delayed: fatigue, arthralgia/myalgia, stomatitis, hand-foot syndrome |
| Lorlatinib (Lorbrena) | 100 mg orally once daily | Acute: diarrhea Delayed: edema, peripheral neuropathy, cognitive effects, hypertension, hyperglycemia, hypercholesterolemia, pneumonitis |
| Midostaurin (Rydapt) | 50-100 mg orally twice daily with food | Acute: nausea, vomiting Delayed: myelosuppression, fever, mucositis, prolonged QT interval, pneumonitis (rare) |
| Nilotinib (Tasigna) | 300 or 400 mg orally twice daily without food | Acute: nausea, vomiting, diarrhea Delayed: rash, fatigue, myelosuppression, prolonged QT interval (rare) |
| Osimertinib (Tagrisso) | 80 mg orally once daily | Acute: diarrhea Delayed: myelosuppression, rash, dry skin, nail toxicity, cardiomyopathy (rare), prolonged QT interval (rare) |
| Pralsetinib (Gavreto) | 400 mg orally once daily without food | Acute: diarrhea Delayed: hypertension, hepatotoxicity, musculoskeletal pain, hemorrhage, pneumonitis |
| Regorafenib (Stivarga) | 160 mg orally once daily after a low-fat meal | Acute: diarrhea Delayed: asthenia, hand-foot syndrome, anorexia, hypertension, mucositis, myelosuppression, hepatotoxicity |
| Selpercatinib (Retevmo) | 120 mg orally twice daily (patients < 50 kg) 160 mg orally twice daily (patients >50 kg) | Acute: diarrhea, TLS Delayed: hypertension, prolonged QT interval, hepatotoxicity, hemorrhage |
| Sorafenib (Nexavar) | 400 mg orally twice daily without food | Acute: diarrhea and nausea Delayed: fatigue, hand-foot syndrome, rash, hypertension, hemorrhage |
| Sunitinib (Sutent) | 50 mg orally once daily for 4 weeks followed by 2 weeks rest; 37.5 mg orally daily | Acute: diarrhea and nausea Delayed: hypertension, hand-foot syndrome, rash, yellow discoloration of skin, fatigue, hypothyroidism, mucositis, LV dysfunction, bleeding, hepatotoxicity |
| Tepotinib (Tepmetko) | 450 mg orally once daily with food | Acute: nausea, diarrhea Delayed: edema, fatigue, hepatotoxicity, pneumonitis (rare) |
| Trametinib (Mekinist) | 2 mg orally once daily without food | Acute: rash, diarrhea Delayed: elevated transaminases, lymphedema, cardiomyopathy |
| Vemurafenib (Zelboraf) | 960 mg orally every 12 hours | Acute: nausea, hypersensitivity (rare) Delayed: photosensitivity, rash, arthralgia, alopecia, fatigue, prolonged QT interval, cutaneous squamous cell carcinoma |
| Zanubrutinib (Brukinsa) | 160 mg orally twice daily or 320 mg orally once daily | Acute: diarrhea Delayed: myelosuppression, upper respiratory tract infection, hemorrhage, rash |
| Miscellaneous Agents | ||
| Abiraterone (Zytiga) | 1000 mg orally once daily | Acute: diarrhea, edema Delayed: adrenal insufficiency, hepatotoxicity, joint pain, hypokalemia |
| Adagrasib (Krazati) | 600 mg orally twice daily | Acute: diarrhea, nausea, vomiting Delayed: edema, hepatotoxicity, renal insufficiency, pneumonitis, QT prolongation, hypomagnesemia, hypokalemia |
| Bleomycin (Blenoxane) | 10 units/m2 intravenously on days 1 and 15 every 28 days; 30 units intravenously on days 2, 9, and 16 every 21 days | Acute: hypersensitivity, fever Delayed: skin reaction (rash, hyperpigmentation of skin, striae), mucositis, pneumonitis |
| Bortezomib (Velcade) | 1.3 mg/m2 intravenous bolus or subcutaneously on days 1, 4, 8, 11 followed by a 10-day rest, or weekly for 4 weeks followed by 13-day rest; various doses | Acute: nausea, vomiting, diarrhea Delayed: peripheral neuropathy, fatigue, myelosuppression |
| Dactinomycin (Cosmegen) | 15 mcg/kg or 400-600 mcg/m2 intravenously daily for 5 days; various doses | Acute: nausea, vomiting Delayed: myelosuppression, mucositis, rash, diarrhea, hepatoveno-occlusive disease (rare) |
| Enasidenib (Idhifa) | 100 mg orally once daily | Acute: nausea, vomiting, diarrhea, differentiation syndrome Delayed: hyperbilirubinemia, anorexia |
| Hydroxyurea (Hydrea) | 20-30 mg/kg orally daily; various doses | Acute: none Delayed: myelosuppression |
| Ivosidenib (Tibsovo) | 500 mg orally once daily | Acute: nausea, diarrhea, TLS, differentiation syndrome Delayed: fatigue, arthralgia/myalgia, edema, prolonged QT interval |
| Lenalidomide (Revlimid) | 5-25 mg orally once daily on days 1-21 of 28-day cycle; or continuously | Acute: diarrhea, rash Delayed: myelosuppression, fatigue, VTE, potential for birth defects |
| Mitomycin (Mutamycin) | 6-20 mg/m2 intravenously every 4-8 weeks; 20-40 mg intravesically | Acute: cystitis (intravesically), nausea, vomiting Delayed: myelosuppression, mucositis, anorexia |
| Olaparib (Lynparza) | 300 mg orally twice daily | Acute: nausea, vomiting, diarrhea Delayed: myelosuppression, fatigue, arthralgia/myalgia, pneumonitis (rare) |
| Palbociclib (Ibrance) | 125 mg orally daily on days 1-21 of 28-day cycle | Acute: nausea, vomiting, diarrhea Delayed: stomatitis, alopecia, neutropenia, anemia, thrombocytopenia, transaminitis |
| Sotorasib (Lumakras) | 960 mg orally once daily | Acute: diarrhea, nausea, vomiting Delayed: anemia, hepatotoxicity, pneumonitis |
| Pegaspargase (Oncaspar) | 2000-2500 units/m2 intramuscularly every 14 days | Acute: hypersensitivity Delayed: febrile neutropenia, coagulation abnormalities, hepatotoxicity, pancreatitis |
| Venetoclax (Venclexta) | 20 mg orally daily during week 1; 50 mg daily during week 2; 100 mg daily during week 3; 200 mg daily during week 4; then 400 mg orally daily thereafter; various doses | Acute: diarrhea, nausea, vomiting, TLS Delayed: myelosuppression, upper respiratory infections, fatigue |