Sequential high-dose chemotherapy , or sequential high-dose chemotherapy ( eng. Sequential high-dose chemotherapy ), often used by hematologists and often referred to as "sequencing" is a method of chemotherapy for malignant tumors , consisting in the sequential administration of 2-4 courses of high-dose monotherapy (i.e., therapy with a single drug , not a combination). In addition, in each subsequent course, a different drug is used in the sequence that does not have cross-resistance with the first. It is used mainly in relapsed or primary resistant lymphomas and Hodgkin's lymphoma . [1] [2] Clinical trials of this approach for multiple myeloma (multiple myeloma) are also being conducted. [3]
The idea behind this approach is that with the sequential, rather than simultaneous, prescription of chemotherapy drugs, it is possible to bring the dose of each of them to the maximum tolerable (and thereby increase the effectiveness of therapy), since this does not result in hematological toxicity, inevitable when combining chemotherapy. At the same time, since each course uses a different drug that does not have cross-resistance with the first one, and each of the chemotherapy drugs is entered only once within the sequence, the tumor does not have time to develop the resistance to the chemotherapy drugs used. And if it develops, it will not have clinical significance, since the next drug, “sequence”, having a different mechanism of action, will “knock out” a clone resistant to the previous drug.
Method of application
Prior to the initiation of sequential chemotherapy, the patient should be brought into remission by standard induction schemes, such as DHAP . Sequential chemotherapy is used as a consolidation.
Dosing regimen
| Course | A drug | Acronym of chemotherapy regimen | Dose | Route of administration |
|---|---|---|---|---|
| The first | Cyclophosphamide | HD-CYC or HD-Cyc | ~ 4500-6000 mg / m² | Intravenous infusion |
| Second | Methotrexate | HD-MTX or HD-Mtx | ~ 2500-8000 mg / m² | Intravenous infusion |
| Third | Citarabine | HDAC or HD-AraC | ~ 3000-6000 mg / m² | Intravenous infusion |
| Fourth | Etoposide | HD-ETO or HD-Eto | ~ 1000-2000 mg / m² | Intravenous infusion |
After completing sequential chemotherapy, standard “pre-transplant” combined high-dose chemotherapy (for example, under the BEAM protocol) and autologous hematopoietic stem cell transplantation as consolidation are usually performed.
Depending on the patient’s condition, the type of lymphoma and the tolerability of chemotherapy, one or other components of the sequence (for example, cytarabine, methotrexate or etoposide, or even 2-3 of them) can be skipped or the doses reduced.
Currently, the German researchers, who originally proposed this regime, gradually abandon it, conducting 2 courses of DHAP and then autologous stem cell transplantation immediately, as they believe that there is no evidence that the use of sequential chemotherapy after DHAP improves the results of treatment (indicators of general and disease-free survival), and the toxicity, cost and duration of treatment increase.
Notes
- ↑ High dose sequential chemotherapy and autologous stem cell transplantation in patients with relapsed / refractory lymphoma.
- Results Cologne high-dose sequential chemotherapy in the Hodgkin lymphoma study group of the German Hodgkin Lymphoma Study Group (GHSG).
- ↑ High Dose Sequential Therapy and Autologous Stem Cell Rescue for Multiple Myeloma