Innovative Chemotherapy: Prospective Trial of Individualized Chemotherapy

In: Chemotherapy

22 Nov 2014

Prospective Trial of Individualized Chemotherapy
While several thousand correlations have been performed between the results of in vitro testing and clinical response, relatively few properly conducted prospective clinical trials have been reported. Currently, we are more than halfivay through a prospective clinical trial based on selection of individualized therapy for patients with extensive stage SCLC.W This disease presents unusual problems as well as opportunities for such a trial. While “curative” surgical resections are seldom attempted in the USA, SCLC is often widely metastatic at diagnosis. The number of tumor cells in specimens obtained from route staging procedures are relatively small and contain many stromal cells. However, culture methods exist for the selective propagation of small numbers of tumor cells with quite acceptable success rates.

Using such methods, we selectively increased the number of tumor cells, and performed DST whenever sufficient tumor cells were available. A nonclonogenic assay was utilized, the Weisenthal Dye exclusion assay. Because therapy for SCLC patients cannot be unduly delayed, we treated patients with etoposide/cisplatin for 12 weeks while awaiting the results of DST. Patients in complete response at 12-week restaging were continued on this regimen. Patients with partial or no responses, and those relapsing after complete response, received the in vitro selected “best regimen * (IVBR), a 3-drug combination, as secondary therapy. Specimens were obtained from 79/80 consecutive untreated patients, 55% of which contained tumor cells.

Cell lines were established from 43% of all patients from whom at least 1 tumor-containing specimen was obtained, and most could be tested successfully. Several parameters of the DST data were significantly associated with clinical response to primary therapy and with response to DST selected secondary therapy. Sixteen patients (23%) received IVBR, and 4 of these (25%) attained a complete response, compared to 7% of those receiving empiric therapy.
In summary, these data indicate: 1) while individualized therapy in extensive stage SCLC is possible, it is extremely labor-intensive; 2)DST data are associated with clinical response to primary therapy and DST selected secondary therapy; and 3) individualized therapy may be of modest therapeutic benefit. The situation with NSCLC is more complex. Culture methods are not as well established and are complicated by the multitude of subtypes (not all of which have the same growth requirements). In addition, even when testing is feasible, the tumor cells are chemosensitive to few, if any, drugs. Until more effective therapies are available, DST is reduced to selecting the “best of a bad lot.” A theoretic exception to this may be identification of NSCLC tumors with neuroendocrine markers, a subtype that appears to be more chemosensitive than other NSCLC.

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