Which chemotherapy regimens are effective for different types of cancer?

Chemotherapy Regimen Selection by Cancer Type

Yes, there is a well-established clinical framework matching specific chemotherapy regimens to cancer types based on histology, molecular features, and disease stage, with platinum-based combinations serving as the backbone for most solid tumors and taxane/anthracycline regimens dominating breast cancer treatment.

Lung Cancer

Small Cell Lung Cancer (SCLC)

• Etoposide plus cisplatin (EP) is the standard first-line regimen for all patients with SCLC, replacing older alkylator/anthracycline-based regimens due to superior efficacy and reduced toxicity 1
• Carboplatin may be substituted for cisplatin to reduce emesis, neuropathy, and nephropathy risk, with meta-analysis showing equivalent efficacy (response rate 67% vs 66%, median survival 9.6 vs 9.4 months) 1
• For extensive-stage disease, chemotherapy alone is the recommended treatment, with median survival of approximately 9-10 months 1

Non-Small Cell Lung Cancer (NSCLC)

• After platinum therapy failure: docetaxel 75 mg/m² as single agent every 3 weeks 2
• Chemotherapy-naive disease: docetaxel 75 mg/m² followed by cisplatin 75 mg/m² 2
• Histologic discrimination between adenocarcinoma and squamous cell carcinoma is mandatory, as adenocarcinomas respond favorably to certain agents while squamous cell carcinomas demonstrate greater toxicity with the same regimens 3, 4

Gastrointestinal Cancers

Esophageal and Gastroesophageal Junction (EGJ) Adenocarcinoma

• First-line therapy: trastuzumab with chemotherapy for HER2-positive tumors (IHC 3+ or IHC 2+ with FISH amplification) 1, 5
• Docetaxel 75 mg/m² with cisplatin 75 mg/m² followed by fluorouracil 750 mg/m² per day as 24-hour infusion (days 1-5) 1, 2
• Second-line therapy: ramucirumab as single agent or combined with paclitaxel (category 1 for EGJ adenocarcinoma) 1
• Irinotecan significantly prolongs survival compared to best supportive care (median survival 4.0 vs 2.4 months) 1

Gastric Adenocarcinoma

• Docetaxel 75 mg/m² followed by cisplatin 75 mg/m² (day 1 only), then fluorouracil 750 mg/m² per day as 24-hour infusion (days 1-5) 1, 2
• Trastuzumab with cisplatin and capecitabine or 5-fluorouracil for HER2-overexpressing metastatic disease in treatment-naive patients 5

Colon Cancer

• Initial therapy for metastatic disease in patients appropriate for intensive therapy: FOLFOX (mFOLFOX6), FOLFIRI, CapeOx, infusional 5-FU/LV, capecitabine, or FOLFOXIRI, with or without targeted agents 1
• No single regimen is preferable over others; sequencing shows little difference in clinical outcomes 1
• 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 1
• Available agents include: 5-FU/leucovorin, capecitabine, irinotecan, oxaliplatin, bevacizumab, cetuximab, panitumumab, ziv-aflibercept, ramucirumab, regorafenib, trifluridine-tipiracil, pembrolizumab, and nivolumab 1

Genitourinary Cancers

Bladder Cancer

• Gemcitabine plus cisplatin (GC) is the standard first-line choice for most patients, preferred over MVAC due to similar activity with less toxicity 1, 6
• MVAC (methotrexate, vinblastine, doxorubicin, cisplatin) remains a category 1 recommendation but with higher toxicity 1
• Alternative regimens: cisplatin/paclitaxel, gemcitabine/paclitaxel, gemcitabine/docetaxel, cisplatin/gemcitabine/paclitaxel, carboplatin/gemcitabine/paclitaxel 1
• In patients with glomerular filtration rate <60 mL/min, carboplatin must be substituted for cisplatin in all regimens 1, 6, 3

Castration-Resistant Prostate Cancer (CRPC)

• Docetaxel 75 mg/m² with prednisone 5 mg twice daily continuously for metastatic disease 2

Breast Cancer

Adjuvant Breast Cancer

• Doxorubicin 50 mg/m² plus cyclophosphamide 500 mg/m² followed by either paclitaxel or docetaxel for HER2-overexpressing node-positive or high-risk node-negative disease 5
• Docetaxel 75 mg/m² administered 1 hour after doxorubicin 50 mg/m² and cyclophosphamide 500 mg/m² every 3 weeks for 6 cycles 2
• Trastuzumab as single agent following multi-modality anthracycline-based therapy for HER2-overexpressing tumors 5

Metastatic Breast Cancer

• First-line: paclitaxel combined with trastuzumab for HER2-overexpressing disease 5, 7
• Single-agent trastuzumab for patients who received one or more chemotherapy regimens for metastatic disease 5
• Anthracyclines (doxorubicin, epirubicin) and taxanes (paclitaxel, docetaxel) are the most active agents, with single-agent taxane activity similar to older combination chemotherapy 7
• Capecitabine is indicated for patients who progress after anthracycline and taxane therapy 7
• Third- and fourth-line: vinorelbine and gemcitabine 7

Head and Neck Cancers

Squamous Cell Carcinoma of Head and Neck (SCCHN)

• Induction therapy: docetaxel 75 mg/m² followed by cisplatin 75 mg/m² (day 1), then fluorouracil 750 mg/m² per day as 24-hour infusion (days 1-5) for 4 cycles 1, 2
• Alternative: docetaxel 75 mg/m² followed by cisplatin 100 mg/m² (day 1), then fluorouracil 1000 mg/m² per day as 24-hour infusion (days 1-4) for 3 cycles 1, 2
• Definitive chemoradiotherapy: high-dose cisplatin 100 mg/m² every 3 weeks with radiation therapy (category 1) 1
• Cetuximab with radiation therapy for patients not medically fit for standard chemoradiotherapy (category 1), providing improved locoregional control and median survival (49.0 vs 29.3 months) 1

Metastatic/Recurrent Disease

• Active combination regimens: cisplatin or carboplatin plus 5-FU with cetuximab (category 1), cisplatin or carboplatin plus taxane, cisplatin with cetuximab, or cisplatin with 5-FU 1
• EXTREME trial: cetuximab plus cisplatin/5-FU or carboplatin/5-FU improved median survival compared to chemotherapy alone 1
• Median survival with chemotherapy is approximately 6 months, with 1-year survival rate approximately 20% 1

Endometrial Cancer

High-Risk Disease

• 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 tumors 1
• Combined chemoradiation: cisplatin 50 mg/m² on days 1 and 29 with external-beam radiation followed by carboplatin (AUC 5) plus paclitaxel (175 mg/m²) every 3 weeks for 4 cycles 1
• PORTEC-3 trial: chemoradiation improved 5-year recurrence-free survival (75.5% vs 68.6%) 1

High-Intermediate Risk Disease

• CAP chemotherapy (cyclophosphamide 333 mg/m², doxorubicin 40 mg/m², cisplatin 50 mg/m²) every 4 weeks for 3+ courses showed improved outcomes in subgroup analysis 1

Cancer of Unknown Primary (CUP)

Adenocarcinoma

• Paclitaxel plus carboplatin with or without etoposide is effective for adenocarcinoma of occult primary 1
• Paclitaxel/carboplatin combination: overall response rate 38.7%, median survival 11.0 months, 1-year survival 38% 1
• Triple-drug regimen (paclitaxel, carboplatin, oral etoposide): 1-, 2-, and 3-year survival rates of 48%, 20%, and 14% 1
• Bevacizumab plus erlotinib (with or without paclitaxel/carboplatin): median survival 7.4 months, superior to gemcitabine alone (3 months) 1

Poorly Differentiated Carcinomas

• Cisplatin-based combination chemotherapy: objective response rates 53-63%, complete response rates 12-26% 1
• Patients with undifferentiated carcinomas had better response rate than poorly differentiated adenocarcinomas (79% vs 35%) 1

Critical Patient Selection Factors

Performance Status Requirements

• Combination chemotherapy should only be offered to patients with ECOG performance status 0-2 for most solid tumors 6, 3
• Patients with performance status 3-4 should receive best supportive care only or single-agent therapy 1
• Karnofsky Performance Status ≤60 or ECOG PS ≥3 warrants best supportive care only 1

Organ Function Requirements

• Adequate renal function is mandatory for cisplatin-based combinations; carboplatin substitution required when GFR <60 mL/min 1, 6, 3
• Avoid docetaxel if bilirubin >ULN or if AST/ALT >1.5× ULN with alkaline phosphatase >2.5× ULN 2
• Do not administer docetaxel to patients with neutrophil counts <1500 cells/mm³ 2
• Platelet count ≥100,000/mm³ required for safe carboplatin administration 6

Premedication Requirements

• All patients receiving docetaxel must receive oral corticosteroid premedication to reduce hypersensitivity reactions and fluid retention 2
• Patients receiving trastuzumab require cardiac monitoring with LVEF assessment prior to and during treatment 5

Common Pitfalls to Avoid

• Do not use cisplatin in patients with renal impairment; carboplatin substitution is mandatory when GFR <60 mL/min 1, 6, 3
• Do not administer anthracyclines without cardiac assessment; baseline cardiac function evaluation is essential, and trastuzumab combined with anthracyclines is contraindicated due to severe cardiomyopathy risk 5
• Do not treat nonurothelial bladder carcinomas with standard urothelial regimens; these have limited efficacy and should be treated based on identified histology (adenocarcinomas with colon cancer regimens, squamous tumors with head and neck regimens) 1
• Do not administer chemotherapy to patients with poor performance status (ECOG 3-4) expecting curative outcomes; these patients show poor tolerance and few complete remissions 1, 6, 3