What are the first-line and second-line treatments for different pathologies?

First-Line and Second-Line Treatments for Different Pathologies

Bone Cancer

Chondrosarcoma

• Conventional chondrosarcoma (grades 1-3) has no known standard chemotherapy options as first-line or second-line therapy 1
• For mesenchymal chondrosarcoma, follow Ewing's sarcoma treatment regimens 1
• For dedifferentiated chondrosarcoma, follow osteosarcoma treatment regimens 1

Ewing's Sarcoma

• First-line therapy options (primary/neoadjuvant/adjuvant):

  • VAC/IE (vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide) 1
  • VAI (vincristine, doxorubicin, and ifosfamide) 1
  • VIDE (vincristine, ifosfamide, doxorubicin, and etoposide) 1

• First-line therapy for metastatic disease at initial presentation:

  • CVD (cyclophosphamide, vincristine, and doxorubicin) 1
  • VAC/IE (vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide) 1
  • VAI (vincristine, doxorubicin, and ifosfamide) 1
  • VIDE (vincristine, ifosfamide, doxorubicin, and etoposide) 1

• Second-line therapy (relapsed or refractory disease):

  • Cyclophosphamide and topotecan 1
  • Temozolomide and irinotecan 1
  • Ifosfamide and etoposide 1
  • Ifosfamide, carboplatin, and etoposide 1
  • Docetaxel and gemcitabine 1

Osteosarcoma

• First-line therapy (primary/neoadjuvant/adjuvant or primary therapy for metastatic disease):

  • Cisplatin and doxorubicin 1
  • MAP (high-dose methotrexate, cisplatin, and doxorubicin) 1
  • Ifosfamide and etoposide 1
  • Ifosfamide, cisplatin, and epirubicin 1

• Second-line therapy (relapsed or refractory disease):

  • Docetaxel and gemcitabine 1
  • Cyclophosphamide and etoposide 1
  • Cyclophosphamide and topotecan 1
  • Gemcitabine 1
  • Ifosfamide and etoposide 1
  • Ifosfamide, carboplatin, and etoposide 1
  • High-dose methotrexate, etoposide, and ifosfamide 1
  • Samarium-153 ethylene diamine tetramethylene phosphonate (153Sm-EDTMP) for relapsed or refractory disease beyond second-line therapy 1

Non-Small Cell Lung Cancer

First-Line Therapy

• Platinum-based doublet chemotherapy is the standard first-line treatment for patients with advanced NSCLC 1
• Common regimens include:
  • Cisplatin or carboplatin with paclitaxel 1
  • Cisplatin with vinorelbine 1
  • Cisplatin with pemetrexed (for non-squamous histology) 1
  • Non-platinum combinations (e.g., gemcitabine/docetaxel, gemcitabine/vinorelbine) are reasonable alternatives 1

Maintenance Therapy

• Continuation maintenance:

  • Bevacizumab after platinum-doublet chemotherapy and bevacizumab (category 1) 1
  • Cetuximab after cisplatin, vinorelbine, and cetuximab (category 1) 1
  • Pemetrexed after cisplatin and pemetrexed chemotherapy (for non-squamous histology) 1
  • Gemcitabine after platinum-doublet chemotherapy 1

• Switch maintenance:

  • Pemetrexed after first-line platinum-doublet chemotherapy (for non-squamous histology) 1
  • Erlotinib after first-line platinum-doublet chemotherapy 1
  • Docetaxel after first-line platinum-doublet chemotherapy (for squamous cell carcinoma, category 2B) 1

Second-Line Therapy

• Established second-line agents for disease progression during or after first-line therapy:
  • Docetaxel (superior to vinorelbine or ifosfamide) 1
  • Pemetrexed (considered equivalent to docetaxel with less toxicity in adenocarcinoma and large cell carcinoma) 1
  • Erlotinib (superior to best supportive care) 1

Third-Line Therapy

• Erlotinib is superior to best supportive care 1

Hodgkin Lymphoma

Second-Line Chemotherapy

The selection of second-line chemotherapy depends on the pattern of relapse and previously used agents. Options include:

• ICE (ifosfamide, carboplatin, and etoposide) 1
• C-MOPP (cyclophosphamide, vincristine, procarbazine, and prednisone) 1
• ChlVPP (Chlorambucil, vinblastine, procarbazine, and prednisone) 1
• DHAP (dexamethasone, cisplatin, and high-dose cytarabine) 1
• ESHAP (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin) 1
• GVD (gemcitabine, vinorelbine, and liposomal doxorubicin) 1
• IGEV (ifosfamide, gemcitabine, and vinorelbine) 1
• Mini-BEAM (carmustine, cytarabine, etoposide, and melphalan) 1
• MINE (etoposide, ifosfamide, mesna, and mitoxantrone) 1
• VIM-D (etoposide, ifosfamide, mitoxantrone, and dexamethasone) 1
• GCD (gemcitabine, carboplatin, and dexamethasone) 1

Cutaneous Melanoma

Second-Line or Subsequent Therapy

For patients with previously treated metastatic melanoma, options include:

• BRAF-targeted therapies (for BRAF V600 mutation-positive patients):

  • Dabrafenib/trametinib 1
  • Vemurafenib/cobimetinib 1
  • Encorafenib/binimetinib 1
  • BRAF inhibitor monotherapy (only with contraindications to combination therapy) 1

• Immune checkpoint inhibitors:

  • Nivolumab 1
  • Pembrolizumab 1
  • Nivolumab/ipilimumab combination 1
  • Ipilimumab (particularly if not used in first-line) 1

• Other options:

  • Interleukin-2 (for selected patients) 1

Cervical Cancer

First-Line Therapy for Metastatic/Recurrent Disease

• Paclitaxel and cisplatin combined with bevacizumab is the preferred first-line regimen for metastatic or recurrent cervical cancer based on efficacy and toxicity profile (category I, A) 1

Second-Line Therapy for Metastatic Disease

Multiple options with modest activity:

• Bevacizumab 1
• Topotecan 1
• Vinorelbine 1
• Gemcitabine 1
• Albumin-bound paclitaxel 1
• Docetaxel 1
• Pemetrexed 1
• Irinotecan 1
• Pegylated liposomal doxorubicin 1

Waldenstrom Macroglobulinemia

First-Line Therapy

Based on specific conditions:

• For transplantation candidates:

  • With cytopenias: DRC (dexamethasone, rituximab, and cyclophosphamide) or rituximab + thalidomide 1
  • With high M-protein: R-CHOP or DRC 1

• For non-transplantation candidates:

  • With cytopenias: DRC or rituximab + thalidomide 1
  • With high M-protein: Nucleoside analogs + rituximab; nucleoside analogs + rituximab + cyclophosphamide 1

• For patients with comorbidities:

  • Low M-protein and cytopenias: Rituximab 1
  • Older age and slow progression: Chlorambucil 1

Salvage Therapy

• Alkylator agents: Chlorambucil 1
• Nucleoside analogs: Cladribine or fludarabine 1
• Monoclonal antibody: Rituximab (standard or extended schedule), Alemtuzumab 1
• Nucleoside analogs plus alkylators: Cladribine or fludarabine plus cyclophosphamide 1
• Nucleoside analogs plus rituximab: Fludarabine plus rituximab 1
• Nucleoside analogs plus alkylators and rituximab: Various combinations 1
• Combination chemotherapy plus rituximab: CHOP and rituximab 1
• Other options: Thalidomide, Bortezomib, Stem-cell transplantation 1

Testicular Cancer (Nonseminoma)

First-Line Therapy

• For good-risk (Stage IIA/B): BEP (bleomycin, etoposide, cisplatin) for 3 cycles or EP (etoposide, cisplatin) for 4 cycles 1
• For intermediate-risk (Stage IIC): BEP for 4 cycles 1
• For poor-risk (Stage IIIC): BEP for 4 cycles or VIP (etoposide, ifosfamide, cisplatin) for 4 cycles if bleomycin cannot be tolerated 1

Second-Line Therapy

Options depend on prognostic factors:

• For favorable prognosis: Conventional-dose chemotherapy 1
• For unfavorable prognosis: High-dose chemotherapy with stem cell support, clinical trial, or conventional-dose second-line therapy (VeIP or TIP) 1

Important Considerations

• Treatment selection should be guided by patient-specific factors including disease stage, histology, molecular characteristics, prior treatments, and comorbidities 1
• Fertility preservation should be addressed before commencing chemotherapy, particularly in bone cancer patients 1
• Clinical trials should be considered for all cancer patients, especially those with poor-risk disease or who have failed standard therapies 1
• For most pathologies, care should ideally be delivered by multidisciplinary teams with expertise in managing these specific diseases 1
• Long-term follow-up and surveillance are essential to monitor for disease recurrence and address potential late effects of treatment 1