Efficacy and Late Effects of Stanford V Chemotherapy and Radiotherapy in Untreated Hodgkin’s Disease: Mature Data in Early and Advanced Stage Patients.

Abstract

Abstract From 5/89 to 5/01, 256 patients (pts) with classical Hodgkin’s disease were treated on prospective trials with the weekly Stanford V (doxorubicin, vinblastine, mustard, vincristine, bleomycin, etoposide, prednisone) regimen +/− radiotherapy (RT). Pts with non-bulky stage I-IIA disease received 8 weeks Stanford V + 30 Gy involved field RT (G4 protocol, n=87) at Stanford (n=52) or Northern California Kaiser Permanente (n=35). Pts with bulky stage II (mediastinal mass > 1/3 intrathoracic diameter) or III,IV disease received 12 weeks Stanford V + 36 Gy to sites >=5 cm or macroscopic splenic disease (G2,3 protocol, n =169) at Stanford University. Bulky mediastinal pts received mediastinal, hilar and bilateral supraclavicular RT but no axillary or high neck RT to sites <5 cm. Chemotherapy was supported as needed by G-CSF to maintain dose intensity after the first dose reduction (absolute neutrophil count [ANC] < 1000/mm3) or treatment delay (ANC < 500/mm3). The median age was 29 years (range 16–60) and 134 pts were male. Two pts did not complete treatment: 1 due to sclerosing cholangitis not appreciated at diagnosis and 1 due to hyponatremia plus gastrointestinal toxicity. No cases of clinical bleomycin toxicity or radiation pneumonitis were observed. Major acute toxicities were grade 3–4 neutropenia and constipation. With a median follow-up of 5.7 years for early stage and 6.9 years for advanced stage pts, the outcome and late effects data are detailed in the table below. Among 24 pts with disease progression (4 with early stage and 20 {8 with international prognostic score >=4} with advanced stage disease, 16 (67%) were successfully treated with second-line therapy. Eleven pts have died: 6 from Hodgkin’s disease and 1 each from suicide, complications of second-line transplantation, influenza, lung cancer, and unknown cause. No cases of secondary myelodysplasia/leukemia or non-Hodgkin’s lymphoma have occurred. Second cancers included 1 prostate (no pelvic RT), 1 colon ( no abdominal RT but TBI used with second-line transplant), 1 lung (no RT) and 2 breast (1 with DCIS after mediastinal RT, 1 after axillary RT for >10 cm mass). To date, 72 post-treament conceptions (excluding pre-treament semen or embryo cryopreservation) were recorded with 65 live births (+ 4 current pregnancies) among 34 men and 30 women. In our hands, the Stanford V + RT regimen was effective with modest toxicity and 25% pts conceived post-treatment. An international score >=4 was the major adverse prognostic factor; the majority of relapses were successfully treated secondarily. These data support definitive testing of this treatment program as in the ongoing E2496 Intergroup Study for bulky and advanced stage disease. Efficacy and Late Effects All patients Favorable I, II Bulky I, II III. IV n=256 n=87 n=61 n=108 *[95% confidence intervals] FFP / 4 yr 91% [87–95]* 96% [92–100] 92% [85–98] 86% [79–93] FFP / 8 yr 91% [91–94] 96% [92–100] 92% [85–98] 86% [79–93] FFP / 12 yr 89% [84–94] NA 92% [85–98] 83% [75–92] OS / 4 yr 97% [94–99] 98% [94–100] 98% [93–100] 95% [91–99] OS / 8 yr 95% [92–98] 98% [94–100] 92% [82–100] 95% [91–99] OS / 12 yr 95% [92–98] NA 92% [82–100] 95% [91–99] AML/MDS 0 0 0 0 Solid tumor 5 2 0 3