Karyotype of leukemia cells consistently predicts for response to therapy and survival following salvage therapy in acute myeloblastic leukemia.
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Adult↗
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Results for “Salvage Therapy”
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Salvage therapy for patients with non-Hodgkin's lymphoma.
The non-Hodgkin's lymphomas represent a diverse group of lymphoproliferative disorders for which treatment must be specified according to the patient's status as well as the disease status. Although many advances have been made in the front-line treatment of non-Hodgkin's lymphomas, more than 50% of the patients will not be cured with their initial therapy. Because of these treatment failures with front-line therapy, many different salvage therapies have been tried in this patient population. In this article, we describe several conventional-dose, salvage chemotherapies and strategies for dose escalation and hematopoietic stem cell transplantation in an attempt to overcome chemotherapy resistance.
Antineoplastic Combined Chemotherapy Protocols↗
Predictive factors for effective salvage therapy of nonseminomatous germ cell tumors of testis.
Twenty-four patients with metastatic and chemotherapy-refractory nonseminomatous germ cell tumors of the testis were treated with various chemotherapy regimens upon failure. Eight of the 24 patients (33%) are alive and disease-free after salvage therapy with a median follow-up of sixteen months. Prognostic factors tested included those known to be predictive for initial response to therapy (clinical stage and degree of elevation of the biomarkers). In addition, time to initiation of salvage therapy and response to initial chemotherapy were assessed as variables. Our data suggest that patients with solitary organ metastases following relapse, and response to initial chemotherapy are favorable predictors for response to salvage treatment. All the patients with solitary organ metastases (5/5 [100%]) but only 3/19 (16%) of the patients with multiple metastatic sites were salvaged. Patients with delayed initiation of salvage therapy had a reduced likelihood of achieving a complete remission but this was not statistically significant. The variables identified need to be incorporated into future trials testing the efficacy of salvage therapy for patients with nonseminomatous tumors of the testis.
Antineoplastic Combined Chemotherapy Protocols↗
Intraperitoneal chromic phosphate P 32 as salvage therapy for persistent carcinoma of the ovary after surgical restaging.
From 1977 through 1984, 23 patients with persistent epithelial carcinomas of the ovary received intraperitoneal instillation with chromic phosphate P 32 suspension as salvage therapy after second- or third-look laparotomy. Patients received a median 10 cycles of chemotherapy before chromic phosphate P 32. Disease consisted of microscopic residual only in 10 patients (43%), macroscopic residual that was completely resected in eight (35%), and macroscopic residual disease in which the largest diameter was less than 0.5 cm in five patients (22%). Ten patients are free of disease at 13 to 94 months after chromic phosphate P 32 salvage therapy. Life table survival is 75% at 2 years and 57% at 4 years, with a disease-free survival rate of 54% at 2 years and 27% at 4 years. Patients with no gross residual disease had median disease-free survival of 27 months versus 9 months for patients with macroscopic residual disease (p greater than 0.1). Only three patients (13%) developed surgical bowel complications related to chromic phosphate P 32. Compared with previous studies, intraperitoneal chromic phosphate P 32 as salvage therapy for patients with minimal residual ovarian carcinoma defined at secondary surgical evaluation results in comparable survival and fewer complications than does salvage abdominopelvic irradiation and should be considered as an option to further chemotherapy in selected patients.
Actuarial Analysis↗
Salvage therapy for patients with relapsed or refractory aggressive non-Hodgkin's lymphoma.
Marrow transplantation as salvage therapy in non-Hodgkin's lymphoma seems to be superior to chemotherapy administered in conventional doses, although trials are ongoing. Transplantation results are better when refractory and relapsed patients respond to conventional salvage therapy (sensitive relapse) and residual disease is reduced to a minimum. The authors summarize clinical findings to date, including the latest work with interferon and monoclonal antibodies.
Antineoplastic Combined Chemotherapy Protocols↗
Salvage therapy for metastatic disease.
Available evidence supports the use of the combination of mitomycin plus vinblastine as salvage therapy for metastatic breast cancer. In our experience with 39 patients, this combination is as at least as effective as doxorubicin salvage therapy. In addition, those who respond usually do so within the first 4 weeks of treatment. Trial results show that its safety and toxicity profile was more favorable than doxorubicin-based regimens. In addition, the hematologic toxicities associated with mitomycin can be managed by decreasing the dose and/or prolonging the dosing interval. Most of the patients in this study received full doses of chemotherapy for the duration of the trial. We concluded that mitomycin plus vinblastine is effective and well tolerated in the treatment of metastatic breast disease.
Adult↗
Response to salvage therapy and survival after relapse in acute myelogenous leukemia.
The response to and survival following first salvage therapy regimens for 243 patients with acute myelogenous leukemia (AML) treated between 1974 and 1985 were evaluated. Eighty (33%) patients obtained a complete remission (CR), 24% died prior to achieving a response, and 43% were resistant on their first salvage regimen. The median survival was 18 weeks. Five percent overall and 16% of the CR patients are predicted to survive for more than 5 years. The factor most strongly associated with response and survival was the duration of the initial remission with 49 of 82 (60%) patients whose initial CR duration was at least 1 year in duration obtaining a second CR v 31 of 161 (19%) for patients with a shorter remission (P less than .01). Age, liver function, serum lactic dehydrogenase (LDH), karyotype, and the proportion of blasts plus promyelocytes present at the time of starting salvage therapy were strongly associated with probability of response and survival. Multivariate analysis was used to develop logistic regression and proportional hazard models to predict probability of response and survival, respectively. The major regimens used were conventional-dose cytarabine (ara-C) (combined with anthracyclines or amsacrine), high-dose ara-C, rubidazone, amsacrine (AMSA), other anthracyclines, and autologous or allogeneic transplant programs. After allowing for the prognostic factors in the models, specific treatment regimens were not strongly associated with prognosis.
Adult↗
VP-16 plus ifosfamide plus cisplatin as salvage therapy in refractory germ cell cancer.
Forty-eight evaluable male patients with germ cell tumors (GCT) failing to be cured with first-line therapy were treated with VP-16 (75 mg/m2), ifosfamide (1.2 g/m2), and cisplatin (20 mg/m2) (VIP), all given daily for 5 consecutive days every 3 weeks. All patients either achieved an unresectable partial remission as their best response to induction chemotherapy (Group A), relapsed from complete remission (CR) less than or equal to 2 months after induction therapy (Group B), or had received cisplatin plus VP-16 as previous salvage therapy (Group C). Nine (19%) had extragonadal GCT, and 37 (77%) had advanced disease. Twenty-three (48%) of the patients had greater than or equal 2 prior treatment regimens. Sixteen of 48 (33%) achieved CR with VIP treatment alone or following surgical excision of residual disease. Six of 22 (27%), three of seven (43%), and seven of 19 (37%) patients from groups A, B, and C, respectively, attained a CR. The median survival time of all patients was 7 months (range 0 to 28+) with seven patients remaining continuously free of disease (four patients greater than 1 year). Myelosuppression was significant with a median WBC nadir of 900/mm2 and platelet nadir of 24,000/mm2. Fourteen (26%) had granulocytopenic fever, and renal insufficiency developed in 15%. VIP combination chemotherapy demonstrates activity in this highly unfavorable population of patients with germ cell tumors. The actual contribution of ifosfamide in this regimen is unclear, but these results compare favorably to our experience with similar patients treated with cisplatin plus VP-16 alone. Further studies with VIP as initial salvage therapy for patients with GCT are planned.
Antineoplastic Combined Chemotherapy Protocols↗
Vinblastine, cisplatin and bleomycin as salvage therapy for refractory high-risk metastatic gestational trophoblastic disease.
Vinblastine, cisplatin and bleomycin (VPB) were utilized as salvage therapy in seven women with high-risk metastatic gestational trophoblastic tumors resistant to prior treatment with triple therapy (methotrexate, actinomycin D and cyclophosphamide) or the modified Bagshawe protocol. While four patients (57%) achieved sustained remission with VPB, surgery was performed on two of them to remove sites of resistant disease. The mean prognostic score for the patients who achieved remission was 10 versus 17 for those who died (P less than .05). Although severe hematologic toxicity occurred in five patients (71%), no deaths were attributable to toxicity. Since VPB has limited activity when used as salvage therapy, alternate chemotherapy protocols need to be developed for patients with refractory gestational trophoblastic disease.
Antineoplastic Combined Chemotherapy Protocols↗
Radical hysterectomy as surgical salvage therapy for gynecologic malignancy.
Fourteen patients with recurrent or second primary gynecologic malignancies after pelvic irradiation underwent radical hysterectomy as surgical salvage therapy. Six patients had microscopic regional metastatic disease at the time of surgery. All of these patients died of recurrent tumor. Overall disease-free actuarial survival at five years was 27%; excluding patients with regional metastatic disease, five-year survival was 54%. Complications requiring subsequent major surgical intervention occurred in 29% of patients. There appears to be a limited role for radical hysterectomy as surgical salvage therapy in patients with centrally limited invasive disease after pelvic irradiation.
Adult↗
Salvage therapy in metastatic adult Wilms' tumor.
Adult Wilms' tumor is a rare and aggressive malignancy. Despite multimodality therapy for all stages of disease, the majority of patients develop fatal metastases. Little information is available on effective salvage therapy. The current report describes a 38-year-old man who had Stage I disease. Pulmonary metastases developed after radical nephrectomy and tumor bed irradiation while receiving adjuvant chemotherapy. He achieved a complete remission lasting 8 months with a combination chemotherapy regimen of cyclophosphamide, vinblastine, dactinomycin, and cisplatin. After isolated pulmonary relapse, he received whole-lung irradiation and remained disease-free 4.5 years after diagnosis. The previously reported results of therapy in metastatic or unresectable adult Wilms' tumor are reviewed, and the current case of effective salvage therapy is documented.
Adult↗
Overdose of vinblastine in a child with Langerhans' cell histiocytosis: toxicity and salvage therapy.
The therapeutic index of antineoplastic agents is generally low, therefore, errors in administration can cause severe, life-threatening toxicity. The publication of cases of overdoses may provide useful information on the causes of the mistakes, on drug-induced toxic effects, and on salvage therapy. We report a case of vinblastine overdose in a child affected by Langerhans' cell histiocytosis, Hand-Schüller-Christian syndrome according with the previous classification of histiocytosis X. To our knowledge this is the highest dose of vinblastine ever administered. The child was given salvage therapy with steroids and citrovorum factor. Major side effects were neurologic toxicity (seizures, coma) and marrow aplasia, which improved and gradually resolved beginning day 12.
Adrenal Cortex Hormones↗
Comparison of results of salvage therapy in adult acute myelogenous leukemia.
The results of initial salvage therapy for refractory and relapsed acute myelogenous leukemia for patients treated between 1973 and 1986 have been evaluated. There was no significant improvement in complete remission (CR) rate and survival in patients treated between 1973 and 1980, and the second group between 1981 and 1986. The remission duration was slightly longer in the second time period than in the initial time period. A number of factors were associated with the probability of achieving a CR. The major factors were the age of the patient, duration of the initial CR, liver function test abnormalities, and white blood cell count.
Adult↗
Intraperitoneal recombinant alpha-2-interferon alternating with cisplatin as salvage therapy for minimal residual-disease ovarian cancer: a phase II study.
A phase II study was initiated in March 1987 at the Regina Elena National Cancer Institute of Rome to evaluate the efficacy of alternating intraperitoneal (IP) recombinant alpha-2-interferon (r-alpha 2-IFN) and cisplatin (DDP) as salvage therapy for less than or equal to 5 mm residual-disease (RD) ovarian carcinoma. Fourteen assessable patients entered the study. All had received prior chemotherapy (11 with DDP-based regimens); five patients had macroscopic RD (less than or equal to 5 mm), and nine had microscopic RD (histologically positive random biopsies and/or positive cytology and immunocytochemical tests). The response to IP immunochemotherapy was evaluated by laparotomy. Pathologic complete remissions (PCRs) were achieved in seven patients (50%) who have remained free of disease with a median follow-up of 22+ months (range, 11+ to 30+ months). Six patients achieved a stable disease and one presented disease progression. With the exception of chemical peritonitis-induced adhesions, no limiting toxicity was observed. The results obtained in this small, highly selected series demonstrate that a high PCR rate may be obtained with IP immunochemotherapy with DDP and r-alpha 2-IFN as salvage therapy in residual ovarian carcinoma less than or equal to 5 mm after first-line chemotherapy also including intravenous (IV) DDP. Larger comparative studies must be conducted to establish the potential role of IP DDP and r-alpha 2-IFN as compared with either of the single treatments.
Adult↗
Salvage therapy for radiorecurrent prostate cancer: beyond equipoise - a call for biomarker-driven stratification.
The increasing incidence of localized radiorecurrent prostate cancer demands a shift from modality-centric comparisons toward biomarker-driven patient selection. Light et al. provide a matched comparison of salvage focal therapy (sFT) versus salvage radical prostatectomy (sRP), reporting comparable 10-year cancer-specific survival but fewer complications with sFT. However, the study lacks integration of modern PSMA PET/CT restaging and genomic risk stratification (e.g., Decipher classifier), both of which could profoundly influence therapeutic outcomes. Moreover, salvage reirradiation-a promising third option-is omitted. We argue that equipoise is no longer sufficient; the field needs prospective registries or trials that stratify by imaging and genomic biomarkers, with coprimary endpoints of metastasis-free survival and patient-reported functional outcomes. We also discuss the limitations of PSMA PET/CT for small-volume lesions and the importance of validating genomic thresholds specifically in the salvage setting. Only such an approach will enable truly personalized salvage therapy.
Biomarker stratification↗
Recombinant alpha-interferon as salvage therapy in multiple myeloma. A pilot study.
Ten patients with end-stage multiple myeloma refractory to conventional chemotherapy and hemibody irradiation received recombinant alpha-interferon as salvage therapy. The median duration of treatment was 8 weeks. One patient had an objective response and survived 8 months, whereas in the remaining 9 patients the disease progressed and median survival was 11.5 weeks. Side-effects were substantial and included confusion with extreme weakness, resulting in 5 patients refusing further therapy. The low response rate and the morbidity in this pilot study resulted in its discontinuation and the conclusion that recombinant alpha-interferon as single-agent therapy used for salvage in patients with refractory myeloma is of no value.
Aged↗
Salvage therapy with clindamycin/primaquine for Pneumocystis carinii pneumonia.
Clindamycin/primaquine is effective for treating mild-to-moderate cases of Pneumocystis carinii pneumonia (PCP) in patients with AIDS. We retrospectively reviewed our experience with this combination among patients in whom conventional therapy had failed or was not tolerated. Twenty-six patients who experienced 28 episodes of PCP received salvage therapy with clindamycin/primaquine at two university-affiliated medical centers. Clindamycin was administered intravenously, (usually 900 mg every 8 hours), after which oral therapy was instituted. Primaquine (30 mg) was given orally to all patients except three; two of these patients received 15 mg of the drug daily and another 30 mg of drug on alternate days. In 11 of the episodes, the patients received clindamycin/primaquine as initial therapy for PCP because of previous intolerance of conventional therapy. In 13 of the episodes, conventional therapy had failed or the patients were unable to tolerate the regimen, while in four episodes conventional therapy failed and the patients were unable to tolerate their therapeutic regimens. Twenty-four (86%; 95% confidence interval, 73%-99%) of 28 episodes were successfully treated with clindamycin/primaquine. The most common adverse effect was the development of an erythematous rash. Clindamycin/primaquine appears to be an attractive alternative for patients in whom standard therapy for PCP has failed or cannot be tolerated.
Administration, Oral↗
The role of ifosfamide plus cisplatin-based chemotherapy as salvage therapy for patients with refractory germ cell tumors.
A prospective study of four cycles of etoposide with ifosfamide and cisplatin (VIP) chemotherapy was conducted in 42 germ cell tumor (GCT) patients who were refractory to cisplatin with etoposide/vinblastine-based therapy. Forty patients were evaluable for response. Ten patients (25%) had a complete response: seven to chemotherapy alone and an additional three patients after surgical resection of viable GCT. With a median follow-up of 15 months, four complete responders relapsed, and six patients (15%) remain in remission. Hematologic and nephrotoxicity were moderately severe. Durable complete responses with VIP as second salvage were achieved and suggests that ifosfamide adds efficacy to standard first-salvage therapy. The observed nephrotoxicity and myelotoxicity are considerations in the design of ifosfamide-cisplatin-based regimens. Hematopoietic growth factors may be useful in ameliorating myelotoxicity. The early use of ifosfamide-based chemotherapy may reduce the nephrotoxicity exacerbated by prior cisplatin. A trial of VIP as first salvage after a relapse from a complete response to platinum-based induction therapy is warranted. The modest proportion of patients who achieve a durable remission to VIP as second salvage emphasizes the need for more efficacious salvage therapy for patients who do not achieve a durable complete response.
Adolescent↗