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C S Portlock

Publications and source records attributed to C S Portlock.

At least 19 recordsLinked to original sources
PubMed2004

The NHL-15 protocol for aggressive non-Hodgkin's lymphomas: a sequential dose-dense, dose-intense regimen of doxorubicin, vincristine and high-dose cyclophosphamide.

BACKGROUND: The NHL-15 protocol is a novel, dose-intense, dose-dense, sequential chemotherapy program developed to improve outcome in advanced, aggressive non-Hodgkin's lymphomas. PATIENTS AND METHODS: The phase II NHL-15 protocol comprised: (i) induction [doxorubicin 60 mg/m(2) i.v. on weeks 1, 3, 5 and 7 plus vincristine 1.4 mg/m(2) i.v. (no cap) on weeks 1, 2, 3, 5 and 7]; and (ii) consolidation (cyclophosphamide 3000 mg/m(2) i.v. on weeks 9, 11 and 13 plus granulocyte colony-stimulating factor 5 microg/kg subcutaneous on days 3-10 following each cyclophosphamide dose). Patients with aggressive non-Hodgkin's lymphomas (working formulation: intermediate grade or immunoblastic), bulky stage I and stages II-IV, were eligible. RESULTS: There are 165 eligible patients with a 6.9-year median follow-up (range 0.5-141 months) and a median age of 48 years. For the entire group, 72.1% achieved complete remission, and at 5 years disease-free survival was 57.8% and overall survival (OS) was 62.2%. Ideal dose delivery was >90%. Acute and late toxicities of treatment were manageable and acceptable. Toxic death on treatment was 2.4%. When the diffuse large cell lymphoma histologies were grouped according to the International Prognostic Index (IPI), complete remission and OS in the low-intermediate (LI), and high-intermediate (HI) risk groups were improved by 5%-15% compared with historical CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). This improvement was also noted for LI and HI risk groups in the age-adjusted (aa)IPI analysis for patients < or =60 years of age. CONCLUSIONS: The NHL-15 program can be administered safely and effectively to achieve high rates of durable remission when used for the treatment of advanced stage, aggressive, non-Hodgkin's lymphomas. The 5%-15% improvement in 5-year OS compared with historical CHOP, according to the IPI/aaIPI model (in LI and HI risk groups), is encouraging. Further evaluation and prospective testing of the NHL-15 protocol appears to be warranted.

Adolescent↗
PubMed2001

A 2-step comprehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hodgkin disease: analysis by intent to treat and development of a prognostic model.

Salvage of patients with relapsed and refractory Hodgkin disease (HD) with high-dose chemoradiotherapy (HDT) and autologous stem cell transplantation (ASCT) results in event-free survival (EFS) rates from 30% to 50%. Unfortunately, the reduction in toxicity associated with modern supportive care has improved EFS by only 5% to 10% and has not reduced the relapse rate. Results of a comprehensive 2-step protocol encompassing dose-dense and dose-intense second-line chemotherapy, followed by HDT and ASCT, are reported. Sixty-five consecutive patients, 22 with primary refractory HD and 43 with relapsed HD, were treated with 2 biweekly cycles of ifosfamide, carboplatin, and etoposide (ICE). Peripheral blood progenitor cells from responding patients were collected, and the patients were given accelerated fractionation involved field radiotherapy (IFRT) followed by cyclophosphamide-etoposide and either intensive accelerated fractionation total lymphoid irradiation or carmustine and ASCT. The EFS rate at a median follow-up of 43 months, as analyzed by intent to treat, was 58%. The response rate to ICE was 88%, and the EFS rate for patients who underwent transplantation was 68%. Cox regression analysis identified 3 factors before the initiation of ICE that predicted for outcome: B symptoms, extranodal disease, and complete remission duration of less than 1 year. EFS rates were 83% for patients with 0 to 1 adverse factors, 27% for patients with 2 factors, and 10% for patients with 3 factors (P <.001). These results compare favorably with other series and document the feasibility and efficacy of giving uniform dose-dense and dose-intense cytoreductive chemotherapy and integrating accelerated fractionation radiotherapy into an ASCT treatment program. This prognostic model provides a basis for risk-adapted HDT.

Adolescent↗
PubMed2001

Establishment of a human cell line (SKI-DLCL-1) with a t(1;14)(q21;q32) translocation from the ascites of a patient with diffuse large cell lymphoma.

Cytogenetic abnormalities at chromosome 1q21 are among the most common second genetic events observed in Non-Hodgkin's Lymphomas and have prognostic significance. Recently, BCL9 has been cloned from a pre-B-cell lymphoblastic leukemia cell line, which carried a t(1:14)(q21;q32). However, among a panel of 39 B-cell malignancies with 1q21 translocation, only two cases showed rearrangement for the BCL9 gene. We report the establishment of a new lymphoma cell line from a patient with relapsed diffuse large cell lymphoma. This cell line SKI-DLCL-1 showed cell surface antigens identical to the original tumor and demonstrated the profile of a mature B-cell phenotype: CD19 and CD20 positive, CD5 and C10 negative. It carried a t(1;14)(q21;q32) translocation identical to the original tumor. Although the clinical presentation was an isolated effusion lymphoma, studies for HIV-1, HHV8 and EBV were all negative. Southern blot analysis demonstrated that BCL9 was not rearranged in the SKI-DLCL-1 cell line. In addition, the BCL9 gene was not over-expressed in SKI-DLCL-1 cell line. The identification of a new locus at 1q21 will help clarify the pathogenesis of B-cell malignancies with a translocation involving this locus.

Aged↗
PubMed2000

Granulocyte-colony stimulating factor (G-CSF) may improve disease outcome in elderly patients with diffuse large cell lymphoma (DLCL) treated with CHOP chemotherapy.

Advanced age is an adverse prognostic factor in patients with DLCL. CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) has frequent dose-limiting toxicities, including myelosuppression. We retrospectively reviewed 50 consecutive patients > 60 years of age (median age 72) with B-cell DLCL who received CHOP with G-CSF. Patients received CHOP (median 6 cycles) at three-week intervals. G-CSF was given following all cycles of chemotherapy ("prophylactic G-CSF") in 28 of 50 patients, and following an episode of febrile neutropenia and thereafter in 19 patients, according to ASCO guidelines. Dose intensity, treatment delays, episodes of febrile neutropenia, complete response (CR) rate, disease-free survival, time-to-treatment failure, and overall survival were all analyzed according to the age-adjusted International Prognostic Index (aaIPI). The actual dose intensity for cyclophosphamide was 225.9 mg/m2/week and 0.90, respectively and for doxorubicin was 14.9 mg/m2/week (90% of ideal CHOP dosing for both drugs). Median followup was 4 years for the patients still living. Treatment delays and episodes of febrile neutropenia were less frequent among patients receiving G-CSF with all cycles of CHOP. The CR rates were 100%, 81%, 85%, and 36% for the low, low-intermediate, high-intermediate, and high aalPI risk groups, respectively. The 5-year actuarial relapse-free and overall survival for our patients were comparable to that of the cohort < or = 60 years of age and superior to the > 60 years of age cohort used to establish the aaIPI. With optimization of CHOP dosing, advanced age may not be an adverse prognostic factor for patients with DLCL. The routine use of G-CSF in elderly patients with DLCL should be further investigated.

Actuarial Analysis↗
PubMed1999

The International Prognostic Index predicts for outcome following autologous stem cell transplantation in patients with relapsed and primary refractory intermediate-grade lymphoma.

We analyzed a group of 51 patients with primary refractory and relapsed intermediate-grade lymphoma (IGL) from the time of initiation of three cycles of second-line chemotherapy, ifosfamide, carboplatin and etoposide (ICE), in whom the intent was to administer curative high-dose chemoradiotherapy and autologous stem cell transplantation (ASCT). We sought to determine if the International Prognostic Index (IPI) assessed immediately prior to ICE, second-line IPI (sIPI), was predictive of outcome. The response rate to ICE-based chemotherapy was 69%, and 47% of the transplanted patients remain failure-free at 2.5 years. Stratification of patients based upon the sIPI demonstrated a superior 2.5 year failure-free survival (FFS) curve for patients with low (I) or low-intermediate (II) risk disease vs. those with high-intermediate (III) and high (IV) risk disease (45% vs. 9%, P<0.001). When the analysis was restricted to those patients with chemosensitive disease, the sIPI (I/II vs. III/IV) also separated patients into two distinct prognostic groups (59% vs. 20%, P = 0.04). Patients with sIPI I and II disease have a favorable outcome with ICE chemotherapy and ASCT. However, patients with sIPI III and IV disease derive limited benefit from this treatment strategy, and new approaches are needed in this patient group.

Adult↗
PubMed1999

Ifosfamide, carboplatin, and etoposide: a highly effective cytoreduction and peripheral-blood progenitor-cell mobilization regimen for transplant-eligible patients with non-Hodgkin's lymphoma.

PURPOSE: To evaluate a chemotherapy regimen that consisted of ifosfamide administered as an infusion with bolus carboplatin, and etoposide (ICE) supported by granulocyte colony-stimulating factor (G-CSF) for cytoreduction and stem-cell mobilization in transplant-eligible patients with primary refractory or relapsed non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: One hundred sixty-three transplant-eligible patients with relapsed or primary refractory NHL were treated from October 1993 to December 1997 with ICE chemotherapy at Memorial Sloan-Kettering Cancer Center. Administration of three cycles of ICE chemotherapy was planned at 2-week intervals. Peripheral-blood progenitor cells were collected after cycle 3, and all patients who achieved a partial response (PR) or complete response (CR) to ICE chemotherapy were eligible to proceed to transplantation. Event-free and overall survival, ICE-related toxicity, and the number of CD34(+) cells collected after treatment with ICE and G-CSF were evaluated. RESULTS: All 163 patients were assessable for response, and there was no treatment-related mortality. A major response (CR/PR) was evident in 108 patients (66.3%); 89% of the responding patients underwent successful transplantation. Patient who underwent transplantation and achieved a CR to ICE had a superior overall survival to that of patients who achieved a PR (65% v 30%; P =.003). The median number of CD34(+) cells/kg collected was 8.4 x 10(6). The dose-limiting toxicity of ICE was hematologic, with 29.4% of patients developing grade 3/4 thrombocytopenia. There were minimal nonhematologic side effects. CONCLUSION: ICE chemotherapy, with ifosfamide administered as a 24-hour infusion to decrease CNS side effects, and the substitution of carboplatin for cisplatin to minimize nephrotoxicity, is a very effective cytoreduction and mobilization regimen in patients with NHL. Furthermore, the quality of the clinical response to ICE predicts for posttransplant outcome.

Adolescent↗
PubMed1998

Treatment of mucosa-associated lymphoid tissue lymphoma of the stomach with radiation alone.

PURPOSE: Mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach (MLS) has recently been defined as a distinct clinicopathologic entity, often associated with Helicobacter pylori infection. Many regard antibiotic therapy as the primary treatment of MLS, but in the absence of H pylori infection, or when salvage of antibiotic failures is required, gastrectomy and/or chemotherapy have frequently been used. This study evaluates the efficacy of low-dose radiotherapy alone as an alternative to surgery. PATIENTS AND METHODS: Seventeen patients with stage I to II(2) low-grade MLS without evidence of H pylori infection or with persistent lymphoma after antibiotic therapy of associated H pylori infection were included in this series. Median age was 69 years (range, 39 to 84). Median total radiation dose was 30 Gy (range, 28.5 to 43.5 Gy) delivered in 1.5-Gy fractions within 4 weeks to the stomach and adjacent lymph nodes. Following treatment, all patients underwent endoscopic evaluation and biopsy at a median of 4 months, at 6-month intervals to 2 years, and annually thereafter. RESULTS: All obtained a biopsy-confirmed complete response. At a median follow-up time of 27 months (range, 11 to 68) from completion of radiotherapy, event-free survival was 100%. Treatment was well tolerated, with no significant acute side effects. All remained asymptomatic at last follow-up. CONCLUSION: These results suggest that effective treatment of MLS with low-dose radiation therapy alone is feasible and safe, and allows stomach preservation. Longer follow-up evaluation is required to determine the long-term efficacy of this treatment approach and its side effects. Further studies should clarify the indications for radiotherapy in H pylori-negative or antibiotic-resistant cases of MLS.

Adult↗
PubMed1998

Delphi-panel analysis of appropriateness of high-dose chemotherapy and blood cell or bone marrow autotransplants in diffuse large-cell lymphoma.

Although high-dose chemotherapy and a blood cell or bone marrow autotransplant are commonly used to treat people with diffuse large-cell lymphoma, there is controversy whether this is better than conventional-dose chemotherapy. Subject-selection and time-to-treatment biases preclude comparison of data from uncontrolled trials and there are few date from randomized trials. We used a Delphi-panel group judgment process to determine appropriateness of high-dose chemotherapy and a blood cell or bone marrow transplant. Results were compared to those of randomized trials. Nine lymphoma experts from diverse geographic sites and practice settings were panelists. Boolean MEDLINE searches of lymphoma and chemotherapy and an autotransplant formed the dataset. Panelists were asked to rate appropriateness of high-dose chemotherapy and an autotransplant compared to conventional-dose chemotherapy. Clinical variables were permuted to define 80 clinical settings rated by the panelists on a 9-point ordinal scale. Results were used to determine an appropriateness index reflecting the mean and distribution of ratings. The relationship of appropriateness indices to permuted clinical variables was considered by analysis of variance and recursive partitioning. In people with initial diffuse large-cell lymphoma, autotransplants were never rated appropriate. They were rated uncertain in all settings except in people never receiving chemotherapy and in those with a complete response to chemotherapy and an international prognostic index < 3, where they were rated inappropriate. In people with recurrent lymphoma, autotransplants were rated appropriate in those with a complete or partial response to chemotherapy, uncertain in those with a less than partial response and in those not receiving re-induction chemotherapy and inappropriate in people with CNS lymphoma. These conclusions agree with results of randomized trials.

Aged↗
PubMed1997

Endoscopic ultrasound in the evaluation of gastric small lymphocytic mucosa-associated lymphoid tumors.

PURPOSE: Low-grade, small lymphocytic lymphomas of the mucosa-associated lymphoid tissue (MALT) have recently been shown to be associated with Helicobacter pylori infections. Regression of these tumors has been reported with antibiotic therapy. Here we evaluate endoscopic ultrasound (EUS) as on objective method to evaluate pretreatment disease and posttherapy response. MATERIALS AND METHODS: We retrospectively reviewed 20 patients initially diagnosed elsewhere with MALT lymphoma. All patients had their initial endoscopic biopsies (EGDs) reviewed at Memorial Sloan-Kettering Cancer Center (MSKCC). All patients had EUS performed at the time of consultation and on completion of therapy if treated at our center. Antral biopsies were stained with a modified Steiner preparation to determine infection by H pylori. RESULTS: Gastric low-grade lymphoma was confirmed in 16 of 20 patients; 11 of 16 had previously received antibiotic therapy for biopsy-positive H pylori infection. All gastric lymphomas had an abnormal EUS: eight with discrete tumor masses and eight with gastric wall infiltration (submucosa, n = 4; muscularis propria, n = 3; serosa, n = 1). On completion of lymphoma treatment with chemotherapy, radiotherapy, or surgery, 11 of 16 patients underwent follow-up EUS. Five patients received care elsewhere and did not return for posttreatment EUS. The gastric wall was normal with no evidence of disease on EUS-guided biopsy in eight of 11 patients. The remaining three patients had abnormal gastric walls. One was biopsy-negative and two had residual lymphoma. Four patients were found to have benign lymphoid aggregates in association with H pylori on initial EGD and EUS biopsies. All four patients were previously untreated with antibiotics. EUS showed prominent mucosa, but no significant findings within the gastric wall. CONCLUSION: EUS appears useful to stage objectively and evaluate therapeutic outcome in the management of gastric, low-grade MALT lymphomas. It also helps to distinguish benign lymphoid aggregates from lymphoma associated with H pylori infection. EUS findings may have a significant impact on assessment and therapeutic recommendations.

Adenocarcinoma↗
PubMed1996

Non-Hodgkin lymphoma: contribution of chest CT in the initial staging evaluation.

PURPOSE: To analyze incremental information derived from routinely obtained chest computed tomographic (CT) scans compared with chest radiographs in newly diagnosed non-Hodgkin lymphoma and the effect of this information on staging and therapy. MATERIALS AND METHODS: Abnormalities on chest radiographs and CT scans obtained at specific sites were prospectively identified in 181 consecutive patients with no previous treatment. When discrepant information was found, the effect on staging and treatment was determined. RESULTS: CT and chest radiographic findings were negative in 99 (55%) patients. CT findings were positive and chest radiograph findings were negative in 17 (9%). Both chest radiograph and CT findings were positive in 65 (36%) patients, 16 with identical sites of disease and 49 with more extensive intrathoracic disease at CT. Most stage changes occurred in the diffuse large cell histologic subtype. CONCLUSION: Although routine chest CT findings increased stage of disease in some patients, it had no effect on initial treatment of newly diagnosed non-Hodgkin lymphoma at this institution.

Female↗
PubMed1996

Effect of ABVD chemotherapy with and without mantle or mediastinal irradiation on pulmonary function and symptoms in early-stage Hodgkin's disease.

PURPOSE: To evaluate the effect of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy alone and of ABVD with mantle or mediastinal irradiation (RT) on the pulmonary function of patients with early-stage Hodgkin's disease. PATIENTS AND METHODS: Between 1989 and 1993, 60 patients with clinical stage I to IIIA HD enrolled onto randomized trials at Memorial Sloan-Kettering Cancer Center (MSKCC) underwent prospective evaluation of pulmonary function. All patients received six cycles of ABVD, and 30 patients received mantle or mediastinal RT. Pulmonary function tests (PFTs) and symptom evaluation were conducted before, during, and after completion of chemotherapy and RT, and at various intervals thereafter. The median follow-up time was 30 months. RESULTS: During chemotherapy, symptoms of cough and dyspnea on exertion developed in 32 of 60 patients (53%) and declines in pulmonary function occurred in 22 of 60 patients (37%). Discontinuation of bleomycin was necessary in 14 of 60 patients (23%). Following chemotherapy, there was a significant decline in median forced vital capacity (FVC) and diffusing capacity of carbon monoxide (DLCO). In patients who received mantle or mediastinal RT, there was a further decline in FVC following radiation therapy. At the most recent follow-up evaluation, five of 29 patients (18%) who received ABVD alone and nine of 30 (30%) who received ABVD and RT reported persistent mild pulmonary symptoms (P = .36), which did not significantly affect normal daily activity. CONCLUSION: ABVD chemotherapy induced acute pulmonary toxicity that required bleomycin dose modification in a substantial number of patients. The addition of RT resulted in a further decrease in FVC; however, this did not significantly affect the functional status of patients.

Adolescent↗
PubMed1996

Chemosensitive epidural spinal cord disease in non-Hodgkins lymphoma.

Epidural spinal cord disease (ESCD), an infrequent complication of systemic non-Hodgkins lymphoma (NHL), can occur at diagnosis or at relapse, and is usually treated with radiotherapy, or infrequently surgical decompression. We retrospectively analyzed 140 patients with intermediate-grade NHL (IG-NHL) who were treated on a dose-intense protocol using doxorubicin, vincristine, and high-dose cyclophosphamide (NHL-15). There were seven episodes of ESCD in six (4.3%) patients. Five episodes were asymptomatic at presentation; one patient had back pain, leg numbness, and tingling; and one had radicular pain and mild leg weakness. None had malignant cells in the CSF. One patient received high-dose dexamethasone after laminectomy for diagnostic biopsy; otherwise, dexamethasone was used only as an anti-emetic prior to chemotherapy. Patients who developed ESCD at diagnosis received the planned course of NHL-15 chemotherapy as treatment for ESCD, and those treated with NHL-15 who developed ESCD at relapse were given a regimen containing ifosfamide, carboplatin, and etoposide (ICE). After chemotherapy alone, five of seven episodes showed radiographic resolution of ESCD and improvement of neurologic deficits. One patient received consolidation radiotherapy (2,700 cGy) to the spine after ICE for relapsed ESCD and had a complete response. One patient had progression of systemic lymphoma and ESCD despite chemotherapy. These data suggest that chemotherapy may be effective as initial treatment of ESCD in IG-NHL and may reduce the potential complications of spinal surgery and radiotherapy.

Adult↗
PubMed1993

Accelerated hyperfractionated total-lymphoid irradiation, high-dose chemotherapy, and autologous bone marrow transplantation for refractory and relapsing patients with Hodgkin's disease.

PURPOSE: To evaluate the feasibility and therapeutic effect of accelerated hyperfractionated total-lymphoid irradiation (TLI), high-dose chemotherapy, and autologous bone marrow transplantation (AuBMT) in patients with relapsing or chemotherapy-resistant Hodgkin's disease (HD). PATIENTS AND METHODS: Forty-seven patients with HD who either relapsed after chemotherapy (n = 19), or failed to respond (n = 28) to at least two regimens of combination chemotherapy were studied. No patient received prior radiation therapy (RT). Treatment started with reinduction with standard-dose chemotherapy, followed by involved-field irradiation (15 Gy) to areas of relapsed or persistent disease and TLI (20.04 Gy given in 1.67 Gy fractions three times per day for 4 days). Subsequently, patients received etoposide and high-dose cyclophosphamide, followed by infusion of unpurged autologous bone marrow. All surviving patients had a minimum follow-up duration of 1 year. The median follow-up duration for survivors was 40+ months, and the maximum follow-up duration was 80+ months. RESULTS: Of the 47 patients treated, eight (17%) died of toxicity during the peritransplant period. Twenty-nine of the remaining 39 assessable patients (74%) attained a complete response (CR), while 10 remained with residual disease and progressed early after AuBMT. Four of the CR patients (14%) relapsed and 25 patients remained alive and free of disease. The actuarial disease-free survival (DFS) rate for the entire group at 6.5 years was 50%. Patients who received the protocol for relapsing HD had a significantly better DFS rate (79%) compared with patients treated for continuous refractory disease (DFS, 33%; P < .03). CONCLUSION: Previously unirradiated patients with relapsing or chemotherapy-resistant HD who have exhausted conventional chemotherapy may still respond to an aggressive therapeutic approach consisting of accelerated hyperfractionated TLI, high-dose chemotherapy, and AuBMT rescue. This program offers a potential for long-term DFS to approximately one half of patients who would otherwise have a dismal prognosis with standard-dose salvage therapy.

Adolescent↗
PubMed1992

Management of non-Hodgkin's lymphoma.

This brief review of non-Hodgkin's lymphomas emphasizes aspects of clinical research which have led to important improvements in the management of patients, and examines research questions with relevance for the future. In the intermediate- and high-grade lymphomas, strategies to intensify drug regimens have proved successful in raising rates of curative outcome. With the introduction of growth factors and peripheral stem cell transfusion to support nadir cytopenias it becomes possible to further develop dose-intense regimens. Identification and selection of poor prognostic subsets is key to the further application of these approaches, since the therapeutic ratio may be narrow and up to 50% of patients may be cured with less toxic regimens. In the low-grade lymphomas where a curative outcome is less certain, the application of intensive therapy has proved more controversial and results remain preliminary. Nevertheless, durable remissions appear achievable in advanced-stage CR patients utilizing low-dose consolidative irradiation or autologous transplantation. In contrast to intermediate- and high-grade lymphomas where intensive therapy is often reserved for responding poor-risk presentations, in low-grade lymphoma intensive therapy and consolidation is most successfully applied to good-risk patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Cutaneous T-cell lymphoma presenting with diffuse lymphomatous infiltration of the peripheral nerves: response to combination chemotherapy.

A patient with nonepidermotropic cutaneous T-cell lymphoma presented with severe diffuse peripheral neuropathy that was the result of lymphomatous infiltration of the peripheral nervous system. There was no other evidence of systemic disease. The diagnosis was delayed because of the unusual presentation. A peripheral nerve biopsy was instrumental in establishing the etiology of the neuropathy. The patient achieved complete clinical remission with combination chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

A phase II trial of high-dose cisplatin and dacarbazine. Lack of efficacy of high-dose, cisplatin-based therapy for metastatic melanoma.

Cisplatin and dacarbazine are used widely in the treatment of metastatic melanoma. To evaluate high-dose cisplatin and dacarbazine, 32 patients with metastatic melanoma were treated with cisplatin 50 mg/m2 and dacarbazine 350 mg/m2 daily for three days repeated at 28-day intervals. Their median age was 43.5 years (range, 25 to 73 years), and their median Karnofsky performance status was 80% (range, 70% to 100%). Measurable and evaluable disease sites (number of patients) included lymph nodes (22), lung (17), soft tissue (16), liver (13), bone (seven), spleen (four), adrenal gland (three), skin (three), and other sites (five). Patients received a median of two cycles of therapy (range, one to eight cycles). Thirty patients were evaluable for response. No complete responses were observed. Five patients had a partial response (17%; 95% confidence interval, 3% to 30%) for 16+, 12+, 7, 6.5, and 3 months. Responding sites of disease included lymph nodes (five of 22), lung (three of 17), and soft tissue (two of 16). Hematologic toxicity (Grade greater than or equal to 3) included neutropenia (16 of 32 patients, 30 of 90 cycles), thrombocytopenia (eight of 32 patients, 12 of 90 cycles), and anemia (five patients). Nine episodes of neutropenia and fever were seen in four patients; two had bacteremia. Nonhematologic toxicity (Grade greater than or equal to 3) included hypotension (two patients), nausea and vomiting (four), neuropathy (two), ototoxicity (four), and hypomagnesemia (nine). The low objective response rate and severe toxicity of this regimen preclude its standard use in patients with metastatic melanoma. A review of cisplatin-based therapy in metastatic melanoma suggests that there is no dose-response relationship. The use of high-dose cisplatin (greater than 100 mg/m2) in the treatment of metastatic melanoma is not recommended.

Adult↗