Table 1.
Response assessment of induction chemotherapy in randomized clinical trials
| Study | Tumors | Arms | No. of patients | Induction chemotherapy | Cycles | Criteria | Diagnostic technique | Result | Consequence of response | ||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Head and Neck Contracts Program22 (1987) |
Resectable stage III/IV Oral cavity, hypopharynx, larynx |
IC + S + RT IC + S + RT + S S + RT |
146 155 161 |
Cisplatin Bleomycin | 1 | WHO | Clinicala |
CR 8% PR 40% |
No | ||
| Schuller et al23 (1988) | Stage III/IV HNSCC |
IC + S + RT S + RT |
82 76 |
Cisplatin Methotrexate Bleomycin Vincristine |
3 | WHO? |
Clinicala
Pathological |
CR 19% PR 51% CR 21% |
No | ||
| Jortay et al24 (1990) | T2/3 piriform sinus |
IC + S + RT S + RT |
89 98 |
Vincristine Bleomycin Methotrexate |
1 | NA |
Macroscopic Microscopic |
No tumor shrinkage No histopathologic changes |
No | ||
| VA group2 (1991) | Stage III/IV larynx |
IC + S + RT |
IC + RT S |
166 166 |
Cisplatin 5‐fluorouracil |
2 | WHO (without confirmation ≥4 wk) |
Clinicala
Biopsy of primary tumor area |
CR 31% PR 54% CR 64% |
Third cycle for responders RT for responders and S for nonresponders |
|
| Richard et al25 (1991) | T2‐4 oral cavity / oropharynx |
IC + S ± RT S ± RT |
112 110 |
Vincristine Bleomycin |
12 d (intra‐arterial) |
WHO (without confirmation ≥4 wk) CR: no living tumor cells PR: islets of living tumor cells NR: no modification of tumor cells |
Clinicala
Histopathology of surgical specimen |
Oral cavity: CR + PR 48% Oropharynx: CR + PR 41% Oral cavity: CR + PR 39% Oropharynx: CR + PR 35% |
No | ||
| Paccagnella et al26 (1994) | Stage III/IV oral cavity / oropharynx/ hypopharynx/ paranasal sinus |
IC + RT ± S RT ± S |
118 119 |
Cisplatin 5‐fluorouracil |
1‐4 |
Reevaluation after each cycle CR: total disappearance PR: ≥50% decrease in tumor volume |
NA |
CR 31% PR 49% |
Additional cycle (maximum total 4) | ||
| Volling et al27 (1994) | T2/3oral cavity / oropharynx/ hypopharynx |
IC + S + RT |
IC + RT S |
49 47 |
Carboplatin 5‐fluorouracil |
1 | WHO | Endoscopy and clinical evaluation |
CR 44% PR 18% |
Additional cycle (maximum total 3) RT for responders and S for nonresponders |
|
| Maipang et al28 (1995) | Stage III/IV resectable HNSCC |
IC + S + RT S + RT |
30 24 |
Cisplatin Methotrexate Bleomycin | 2 | WHO (without confirmation ≥4 wk) | Clinical or radiologicala Histopathology of surgical specimen |
CR 30% PR 43% CR 23% PR 53% |
No | ||
| Lefebvre et al9 (1996) | T2‐4 piriform sinus |
IC + S + RT |
IC + RT S + RT |
97 94 |
Cisplatin 5‐fluorouracil |
2 | WHO (with for CR also mandatory complete recovery of larynx mobility) | Endoscopic evaluation (CT recommended) |
CR 54% PR 32% |
Additional cycle (maximum total 3) RT for responders and S + RT for nonresponders |
|
| Lewin et al29 (1997) | Mainly advanced HNSCC |
IC + RT ± S RT ± S |
215 208 |
Cisplatin 5‐fluorouracil |
3 | No evaluation | N/A | N/A | N/A | ||
| Richard et al30 (1998) | T3 larynx |
IC + S + RT |
IC + RT S |
36 32 |
Cisplatin 5‐fluorouracil |
2 | >80% tumor regression | Direct laryngoscopy | Response 40% |
Additional cycle (maximum total 3) RT for responders and S + RT for nonresponders |
|
| Kohno et al31 (2000) | Stage III/IV oral cavity / pharynx | IC + S | IC + RT S | 13 11 | Cisplatin Etoposide Mitomycin C | 1 | WHO | Clinical or radiologicala |
CR 31% PR 23% |
Additional cycle (maximum total 2) RT for responders and S for nonresponders |
|
| Domenge et al32 (2000) | T2‐4 oropharynx | IC + S and/or RT S and/or RT | 157 161 |
Cisplatin 5‐fluorouracil |
1 | WHO? |
Clinical CT (after third cycle)a |
CR 20% PR 36% |
After first: additional cycle unless tumor progression ≥25 After second: additional cycle if tumor regression |
||
| Licitra et al33 (2003) | T2‐4 oral cavity | IC + S S | 98 97 |
Cisplatin 5‐fluorouracil |
2 | WHO | Clinicala Pathological |
CR 33% PR 49% CR 27% PR 18% |
Additional cycle (maximum total 3) – |
||
| Urba et al12 (2006) | Stage III/IV larynx | IC + | C + RT S | C S | 73 19 |
Cis/carboplatin 5‐fluorouracil |
1 | WHO | Clinicala | CR + PR 75% |
Concurrent chemoradiation for responders Surgery for nonresponders |
| Vermorken et al34 (2007) | Stage III/IV unresectable HNSCC | IC + RT | 177 181 |
Docetaxel Cisplatin 5‐fluorouracil Cisplatin 5‐fluorouracil |
1 | WHO (without confirmation ≥4 wk) | Clinical | Additional cycle (maximum total 4) unless progressive disease | |||
| Lefebvre et al10 (2009) | T3‐4 larynx T2‐4 hypopharynx | Alternating C + RT IC C+ RT S + RT | 224 226 |
Cisplatin 5‐fluorouracil |
2 |
CR: complete disappearance of all macroscopic disease, with complete recovery of larynx mobility PR larynx: substantial regression of tumor volume, with complete disappearance of bulging valleculae, bulging of hypothyroid membrane, deep invasion of preepiglottic space, and at least partial recovery of larynx mobility PR hypopharynx: substantial regression of tumor volume, with at least partial recovery of larynx mobility |
CT / MRI Endoscopy under general anesthesia |
CR + PR 85% |
Additional cycle (maximum total 2) RT for responders and S + RT for nonresponders |
||
| Lorch et al35 (2011) | Stage III/IV HNSCC | IC + CRT | 255 246 |
Docetaxel Cisplatin 5‐fluorouracil Cisplatin 5‐fluorouracil |
3 | No evaluation | N/A | N/A | N/A | ||
| Lefebvre et al36 (2013) | Stage III/IV larynx / hypopharynx | IC | C + RT Ctx + RT S | 60 56 23 |
Docetaxel Cisplatin 5‐fluorouracil |
3 | ≥50% regression of primary tumor volume or recovered larynx mobility |
CT / MRI Endoscopy under general anesthesia |
85% | CRT for responders and S + RT for nonresponders | |
Abbreviations: CR, complete response; CRT, chemoradiotherapy; Ctx, cetuximab; HNSCC, head and neck squamous cell carcinoma; IC, induction chemotherapy; NA, not available; N/A, not applicable; NR, nonresponders; PR, partial response; RT, radiotherapy; S, surgery; WHO, World Health Organization.
a
Not further defined / specified.