autologous blood and marrow transplantation - Blog Science ...

380 Chapter 7: Solid Tumors
Preparative regimens
The initial regimen tested was 120-hour infusion carboplatin (1500 mg/m 2
) and
bolus mitoxantrone (75 mg/m 2
) and cyclophosphamide (120 mg/kg). Because
nonhematologic toxicity appeared greater in a retrospective analysis of patients
with an AUC equivalent dose >30, and the median AUC dose was calculated to be
27.5, as of May 1996, all subsequent patients received carboplatin dosing at an
AUC of 28. For platinum-resistant disease, a small cohort of patients (14) were
treated with the same chemotherapy combined with escalating doses of
cyclosporine in an attempt to inhibit multidrug and platinum resistance. However,
the nonhematologic toxicity was too great to move this into a phase II trial.
Subsequent platinum-resistant patients have received treatment on a non-platinum-
containing regimen: split dose bolus melphalan (180 mg/m 2
) and mitoxantrone (90
mg/m 2
) and paclitaxel as a continuous infusion over 4 days (400-650 mg/m 2
).
Finally, starting in May 1996, all platinum-sensitive patients were treated with
paclitaxel (700 mg/m 2
) given over 24 hours, mitoxantrone similar to above (90
mg/m 2
), and carboplatin at an AUC of 28 over 5 days. The inclusion of paclitaxel
was based on its favorable effect in the initial management of this disease and its
in vitro favorable dose-response curve.
All patients treated after 1994 received blood stem cell grafts rather than bone
marrow. Stem cells were universally mobilized by cytokines alone, with a target
dose of 4X10 6
CD34/kg, which provides rapid neutrophil and platelet engraftment.
RESULTS
Patient characteristics
The patient characteristics of the 164 patients are shown in Table 1. The
differences of this group from an unselected group with this disease: only 12% had
stage I or II at diagnosis, 70% had optimal cytoreduction at the time of initial
surgery, and only 40% had either a clinical or pathologic CR to initial therapy. The
median time from diagnosis to transplant was 16 months, and nearly one-half had
bulky disease (>1 cm) at the time of transplant. The median number of
chemotherapy regimens before transplant was two, and at the time of transplant
53% of the patients were platinum resistant. At the time of this analysis the median
follow-up time posttransplant was 36 months. The number of patients treated with
each regimen were 79 for carboplatin, mitoxantrone, and cyclophosphamide; 40 for
melphalan, mitoxantrone and paclitaxel; and 38 for paclitaxel, carboplatin and
mitoxantrone. Seven received a variety of alternative regimens including thiotepa,
cisplatin, and cyclophosphamide on a Southwest Oncology Group (SWOG)
multicenter phase II trial.