What are the different types of chemotherapy regimens used to treat various types of cancer, including solid tumors and hematologic malignancies?

Types of Chemotherapy

Classification by Mechanism of Action

Chemotherapy agents are categorized into several major classes based on their mechanism of action: alkylating agents, antimetabolites, anthracycline antibiotics, plant alkaloids (including microtubule inhibitors), and platinum-based compounds. 1

Alkylating Agents

• Cyclophosphamide is indicated for malignant lymphomas (Stages III-IV), Hodgkin's disease, multiple myeloma, chronic and acute leukemias, mycosis fungoides, neuroblastoma, ovarian adenocarcinoma, retinoblastoma, and breast carcinoma 2
• Dosing ranges from 1-5 mg/kg orally once daily for both initial and maintenance therapy in adults and pediatric patients 2
• For minimal change nephrotic syndrome in pediatric patients, the recommended dose is 2 mg/kg orally once daily for 8-12 weeks (maximum cumulative dose 168 mg/kg) 2

Antimetabolites

• Methotrexate is used for acute lymphoblastic leukemia (including CNS prophylaxis and treatment), lymphomas (Burkitt's tumor, lymphosarcomas), mycosis fungoides, and osteosarcoma 3
• For intrathecal administration in meningeal leukemia, age-based dosing is superior to body surface area dosing: <1 year (6 mg), 1 year (8 mg), 2 years (10 mg), ≥3 years (12 mg) 3
• High-dose methotrexate for osteosarcoma starts at 12 g/m² IV as a 4-hour infusion, escalating to 15 g/m² if peak serum concentrations don't reach 1,000 micromolar 3

Anthracycline Antibiotics

• Doxorubicin is a key component of multiple combination regimens, including 30 mg/m²/day IV for 3 days in osteosarcoma protocols 3
• Used in combination with cyclophosphamide for breast cancer and as part of CHOP regimens for lymphomas 4, 2

Plant Alkaloids and Microtubule Inhibitors

• Paclitaxel demonstrates dose-dependent efficacy: 175 mg/m² IV over 3 hours showed superior outcomes compared to 135 mg/m² in metastatic breast cancer 4
• Docetaxel at 75 mg/m² plus cisplatin 75 mg/m² is recommended for esophageal and gastroesophageal junction adenocarcinoma 5
• Vinorelbine 25-30 mg/m²/week plus cisplatin produces grade 3-4 neutropenia in 78-82% of patients with NSCLC 4

Platinum-Based Compounds

• Etoposide plus cisplatin (EP) is the standard first-line regimen for small cell lung cancer, replacing older alkylator/anthracycline-based regimens due to superior efficacy and reduced toxicity 4, 5
• Carboplatin may substitute for cisplatin with equivalent efficacy (response rate 67% vs 66%, median survival 9.6 vs 9.4 months) but carries greater myelosuppression risk 4
• Carboplatin substitution is mandatory when glomerular filtration rate <60 mL/min 5

Disease-Specific Combination Regimens

Testicular Cancer

• Stage IB-IIB (good-risk): EP for 4 cycles or BEP (bleomycin/etoposide/cisplatin) for 3 cycles 6
• Stage IIC-III (intermediate-risk): BEP for 4 cycles 6
• Stage IIIC (poor-risk): BEP for 4 cycles or VIP (etoposide/ifosfamide/cisplatin) for 4 cycles in selected patients 6
• Second-line therapy: VeIP or TIP (paclitaxel/ifosfamide/cisplatin) for conventional-dose therapy; high-dose carboplatin plus etoposide with stem cell support for unfavorable prognosis 4
• Palliative/refractory disease: Gemcitabine plus oxaliplatin or gemcitabine plus paclitaxel 4

Small Cell Lung Cancer

• Extensive-stage disease: Etoposide plus platinum (cisplatin or carboplatin) as standard regimen, with median survival 9-10 months 4, 5
• Irinotecan plus cisplatin showed initial promise in Japanese trials (median survival 12.8 vs 9.4 months) but subsequent US trials failed to confirm superiority 4

Non-Small Cell Lung Cancer

• First-line therapy: Paclitaxel 135 mg/m² IV over 24 hours with cisplatin 75 mg/m² produces grade 3-4 neutropenia in 75% of patients 4
• Alternative regimens: Gemcitabine 1000 mg/m²/week × 3 plus cisplatin 100 mg/m² every 4 weeks (grade 3-4 neutropenia 57%, anemia 25%) 4
• Docetaxel 75 mg/m² plus cisplatin 75 mg/m² for unresectable stage IIIB-IV disease 4

Colorectal Cancer

• First-line metastatic disease: FOLFOX (mFOLFOX6), FOLFIRI, CapeOx, infusional 5-FU/LV, capecitabine, or FOLFOXIRI with or without targeted agents 5
• FOLFOX regimen: Oxaliplatin 85 mg/m² IV over 2 hours on day 1 plus leucovorin 200 mg/m² IV over 2 hours followed by fluorouracil 400 mg/m² bolus and 600 mg/m² IV over 22 hours on days 1-2 every 2 weeks (grade 3-4 neutropenia 53%) 4
• FOLFIRI: Irinotecan 125 mg/m² plus fluorouracil-leucovorin IV days 1-2 every 2 weeks (grade 3-4 neutropenia 54%) 4
• Combined analysis of 7 phase III trials demonstrates correlation between increased median survival and administration of all 3 cytotoxic agents (5-FU/LV, oxaliplatin, irinotecan) at some point during treatment 5

Breast Cancer

• Node-positive adjuvant therapy: Cyclophosphamide 600 mg/m², doxorubicin 60-90 mg/m² plus G-CSF every 3 weeks × 4 followed by paclitaxel 175 mg/m² every 3 weeks × 4 4
• Metastatic disease: Capecitabine 1250 mg/m² bid × 2 weeks every 3 weeks plus docetaxel 75 mg/m² every 3 weeks × 6 (grade 3-4 neutropenia 69%) 4
• High-risk endometrial cancer: Carboplatin (AUC 5-6) plus paclitaxel (175 mg/m²) every 3 weeks is the most commonly used regimen for serous tumors and stage III or higher 5

Acute Myeloid Leukemia

• Induction regimens: Standard-dose cytarabine plus anthracycline (7+3), MEC (mitoxantrone/cytarabine/etoposide), ICE (idarubicin/cytarabine/etoposide), FLAG (fludarabine/cytarabine/G-CSF), or FLAG-IDA 4
• BPDCN (Blastic Plasmacytoid Dendritic Cell Neoplasm): Hyper-CVAD achieves 80% CR rate with superior outcomes compared to AML-type regimens (median OS 28.3 vs 7.1 months) 4

Ovarian Cancer

• Germ cell tumors with residual/recurrent disease: TIP (paclitaxel/ifosfamide/cisplatin), VAC (vincristine/dactinomycin/cyclophosphamide), VeIP (vinblastine/ifosfamide/cisplatin), or VIP (etoposide/ifosfamide/cisplatin) 4
• Sex cord-stromal tumors (high-risk stage I): Platinum-based chemotherapy (category 2B recommendation) 4

Head and Neck Cancer

• Induction therapy: Docetaxel 75 mg/m² followed by cisplatin 75 mg/m² (day 1), then fluorouracil 750 mg/m²/day as 24-hour infusion (days 1-5) for 4 cycles 5
• Definitive chemoradiotherapy: High-dose cisplatin 100 mg/m² every 3 weeks with radiation therapy (category 1) 5
• Metastatic/recurrent disease: Most active combinations include cisplatin or carboplatin + 5-FU + cetuximab, cisplatin or carboplatin + taxane, or cisplatin + cetuximab 6

Cancer of Unknown Primary

• Adenocarcinoma: Paclitaxel plus carboplatin (overall response rate 38.7%, median survival 11.0 months) with or without etoposide 5
• Squamous cell carcinoma: Paclitaxel + cisplatin + 5-FU, docetaxel + cisplatin + 5-FU, or cisplatin alone 6

Critical Treatment Selection Factors

Performance Status Requirements

• Combination chemotherapy should only be offered to patients with ECOG performance status 0-2 for most solid tumors 5, 6
• Patients with performance status 3-4 should receive best supportive care only or single-agent therapy 5, 6
• Chemotherapy is appropriate for symptomatic patients with PS 1-2 or asymptomatic patients (PS 0) with aggressive cancer 6

Renal Function Considerations

• Adequate renal function is mandatory for cisplatin-based combinations 5, 6
• When GFR <60 mL/min, carboplatin must be substituted for cisplatin in all regimens 5
• For IP/IV chemotherapy in ovarian cancer, patients must have normal renal function, appropriate performance status, and no preexisting neuropathy 6

Hematologic Monitoring

• Platelet threshold ≥100,000/mm³ is required for safe carboplatin administration 6
• ANC threshold ≥1,000/mm³ is typically required for chemotherapy/immunotherapy administration 6
• G-CSF support should be considered for subsequent cycles to prevent recurrent neutropenia, especially in high-risk patients 6

Dose Intensity Considerations

Evidence for Dose Escalation

• Dose-intense chemotherapy without CSF or stem cell support has only shown improved outcomes in consolidative therapy of acute myelogenous leukemia 7
• High-dose chemotherapy with autologous bone marrow transplant improves survival in multiple myeloma and relapsed intermediate/high-grade non-Hodgkin's lymphoma 7
• In solid tumors, many studies suggest less than standard-intensity chemotherapy is suboptimal, but few studies examining higher versus standard doses show significant outcome differences 7

Common Pitfalls

• Hydration is critical: During or immediately after cyclophosphamide administration, adequate fluid intake/infusion is required to force diuresis and reduce urinary tract toxicity risk; therefore, cyclophosphamide should be taken in the morning 2
• Age-based intrathecal dosing: For methotrexate intrathecal administration, age-based dosing produces more consistent CSF concentrations and less neurotoxicity than body surface area-based dosing in patients under 40 years 3
• Leucovorin rescue timing: For high-dose methotrexate, leucovorin 15 mg orally every 6 hours for 10 doses must start at 24 hours after the start of methotrexate infusion 3
• Myelosuppression patterns vary: Gemcitabine-platinum regimens cause grade 3-4 anemia in approximately 25% of patients, while paclitaxel causes grade 4 neutropenia in 75% 4