Can a chemotherapy cycle be delayed in pleural Mesothelioma?

Delaying Chemotherapy Cycles in Pleural Mesothelioma

In most patients with pleural mesothelioma who have already started chemotherapy, delaying cycles is generally not recommended and should be avoided unless there are compelling medical reasons such as severe toxicity or performance status deterioration. 1

Context-Dependent Approach to Chemotherapy Timing

Before Starting Chemotherapy (Treatment-Naïve Patients)

Delaying initiation of chemotherapy may be reasonable only in highly selected asymptomatic patients with epithelial histology, minimal pleural disease burden, and who are not surgical candidates. 1 However, this approach carries significant risks:

• A randomized trial of 43 patients demonstrated that 23% of patients in the delayed treatment group experienced performance status deterioration that precluded any subsequent chemotherapy. 1
• Early chemotherapy provided longer symptom control (25 weeks vs 11 weeks) and a trend toward superior survival (median 14 months vs 10 months; 1-year survival 66% vs 36%), though this did not reach statistical significance (p=0.1). 1
• Chemotherapy should not be delayed and should be considered before the appearance of functional clinical signs (Grade 1C recommendation). 1

Critical caveat: If you choose observation over immediate treatment, close monitoring is mandatory to ensure timely intervention before irreversible performance status decline occurs. 1

During Active Chemotherapy (Between Cycles)

Once chemotherapy has been initiated, cycles should proceed on schedule unless specific contraindications exist:

• Chemotherapy should be stopped or delayed only for: 1
  • Progressive disease
  • Grade 3-4 toxicities
  • Cumulative toxic doses (particularly with cisplatin)
  • Severe performance status deterioration

After Completing 4-6 Cycles

A planned break from chemotherapy is actually recommended after 4-6 cycles in patients with stable or responding disease. 1 This is distinct from "delaying" cycles—it represents completion of the standard treatment course:

• In the pivotal pemetrexed/cisplatin study, 71% of patients completed at least 4 cycles, 53% completed 6 cycles, and only 5% received more than 8 cycles. 1
• Patients with durable disease control can respond to retreatment with the same pemetrexed-based regimen upon progression, making a treatment break after 4-6 cycles both reasonable and evidence-based. 1
• Maintenance chemotherapy is NOT recommended due to insufficient evidence of benefit. 1

Key Clinical Pitfalls to Avoid

1. Do not delay chemotherapy cycles arbitrarily during active treatment—the disease is aggressive and delays risk performance status deterioration that may preclude further treatment. 1

2. Do not confuse a planned treatment break after 4-6 cycles with delaying individual cycles—the former is evidence-based, the latter is not. 1

3. If considering observation before starting any chemotherapy, ensure the patient meets ALL criteria: asymptomatic, epithelial histology, minimal disease burden, not a surgical candidate, and has close monitoring capability. 1

4. Monitor patients on observation extremely closely—nearly one-quarter will deteriorate to the point where they can no longer receive chemotherapy. 1