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The notions of dosage and dose administration methods are very important in chemotherapy.

Massive chemotherapy

The higher the dosage, the more chances we have of killing a great number of cancer stem cells, but also healthy stem cells. Thus, during induction treatment of an acute leukaemia, a massive dosage of anti-mitotic drugs will be used in order to kill every leukaemia stem cell. The normal haematopoietic stem cells (as well as normal skin cells and normal digestive membrane cells) will also be massively struck with:

severe aplasia on the leukocyte lineage, with a major infectious risk requiring solitary confinement in sterile rooms, prophylactic systemic antibiotic therapy and leukocyte growth factor prescription,

severe aplasia on the platelet lineage, with a major risk of diffuse haemorrhage under the skin, in the gut but also in the brain, thus often necessitating platelet transfusion,

mucitis and profuse diarrhoea, often necessitating major rehydration and daily mouth care (sometimes with morphine washings),

complete but reversible alopecia.

Diagram of induction chemotherapy of acute leukaemia There are two possible developments: green: potential remission red: resistant leukaemia The very intensive chemotherapy provokes aplasia necessitating haematological reanimation in a sterile room.

Such very intense chemotherapy can also be used as a closing procedure for certain aggressive solid tumours (lymphoma, testis cancer). It may adminstered under the protection of autologous bone marrow graft (or rather, normal autologous bone marrow stem cells which have been collected before the intensive chemotherapy thanks to the use of haematopoietic growth factors).

A very high chemotherapy dosage may be used since the quasi sterilisation of the bone marrow is salvaged by autologous injection of his/her own haematopoietic stem cells, once all the antimitotic drugs have been metabolised off the bloodstream.

Intensive chemotherapy under the protection of autologous haematopoietic stem cell graft. Intensive chemotherapy under the protection of autologous haematopoietic stem cell graft.The collection of stem cells takes place after a short period of aplasia and recovery through growth factors. After the very intensive chemotherapy, there is a time period during which the serum concentration of the antimitotic drugs is very high. As soon as this concentration decreases, the stem cells can be infused. In the ideal configuration, the tumour is definitively destroyed and the bone marrow repopulates. Without the graft, there would be a risk of permanent aplasia.

In the same manner, for osteosarcoma necessitating high dose methotrexate, such dosage is made possible because an antidote, in the form of folinic acid, can rapidly be injected The methotrexate serum level is regularly measured, and according to this level, different doses of folinic acid are infused. It is evident that such highly efficient treatment requires excellent cooperation between clinicians and a competent pharmacology department.

Successive cures of chemotherapy

The above description is, however, an exception.

Usually, chemotherapy is given in 4 to 6 cures, with a moderately strong dosage, and only provoking moderate aplasia not necessitating specific reanimation (such as antibiotics or platelet transfusions).

This type of chemotherapy is based on the different recovery capacities of normal stem cells and tumour stem cells.

When successive cures are administered, normal stem cells are allowed to recuperate (but also the tumour stem cells). Generally, the normal cells recover much more rapidly and more completely than cancer cells.

The rhythm and the dosage of cures are calculated according to this recovery time (generally a little longer for aged patients) and/or the tumour multiplication rate (shorter for embryonic cancers, longer for colon or typical mammary cancers).

	Diagram of standard anticancer chemotherapy For each cure there is a strong reduction in the number of cancer cells but also slight aplasia. After each cycle, the bone marrow recovers whilst the cancer cells diminish. When cancer cells become resistant, new cycles using the same products do not bring a positive result.